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Test Subject Personal Genetic Analysis ID: 4

Dear Madam! The book you are holding in your hands is a Personal genetic analysis nutriADN which contains an overview of over 150 locations (loci) in your genome, included in 38 analyses. Your Personal genetic analysis consists of four thematic sections, in which you will learn about your genetic susceptibility for the development of cardiovascular diseases, cancers and other diseases, discover your response to certain medications and receive new insights into your genetically determined physical characteristics and abilities. Your individual analysis report will guide you in a clear and intuitive way from the general information, through your personal results, and finally to medical advice and preventive measures. Consequently it will allow you to reduce the risk of developing a disease or will help the disease to be detected early on for timely treatment. Personal genetic analysis nutriADN is designed in accordance with current rules and guidelines for genetic analysis. It follows the recommendations and provisions of the British Human Genetics Commission, intended for the general populous. Great importance is given to the appropriate choice of genetic markers. There is extremely high number of genetic markers available but we include in the analysis only those, which have been proven reliable and for which an appropriate quality of scientific research has been performed. We try to include results of studies with high statistical reliability, which have been performed on a sample set of at least 1000 people, and which have been independently published in other studies. We choose mostly studies which have been published in highly recognized scientific magazines.

Special attention is given to the appropriate compilation of professional advice and preventive measures. Specialized experts in the field of medicine and pharmacy take care of this by giving appropriate guidelines based on genetic information. We also collaborate with a laboratory which operates according to the ISO 17025 standard and where extremely reliable and state-of-art molecular diagnostics technology is used to analyse your DNA. The laboratory is a certified provider of services which are conducted on genotyping platforms produced by the Illumina Company (ÂťIllumina certified providerÂŤ). We are convinced that with the help of your Personal genetic analysis nutriADN you can positively influence your health. We advise you to take into consideration the given preventive measures and medical recommendations, especially for the analyses where your genetic risk is increased. However, we would like you to know that your Personal generic analysis NutriADN does not contain any diagnoses and we recommend that you consult your personal doctor in the case of a great change in your lifestyle.

Your nutriADN team

Contents Genetic testing facts

Interesting genetic facts

How to use the genetic guidebook

Displaying the results for drugs and traits

Displaying results for diseases

Genetic risk for certain diseases Alzheimerâ&#x20AC;&#x2122;s disease

21 24

Asthma 26 Atrial fibrillation

Coeliac disease

Glaucoma 32 Multiple sclerosis

High blood pressure (Hypertension)

Psoriasis 38 Rheumatoid arthritis

Restless leg syndrome

Diabetes mellitus type 1

Diabetes mellitus type 2

Myocardial infarction (Heart attack)

Venous thromboembolism

Gallstones 52

Genetic risk factors for developing cancer

Skin cancer (Basal-cell carcinoma)

Lung cancer

Colorectal cancer

Breast cancer

Medicament response

Clopidogrel - prevention of blood clotting

Metformin - regulation of blood sugar

Omeprazole - inhibition of gastric acid secretion

Perindopril - treatment of stable coronary artery disease

Statins - lowering blood cholesterol

Warfarin - prevention of blood clotting

Genetically determined physical features and traits

Eye colour

Sensitivity to pain

Muscle structure

Nicotine addiction

Resistance to infection with noroviruses

Resistance to malaria (type Duffy)

Perception of bitter taste

Alcohol metabolism

Caffeine metabolism

Lactose metabolism

Episodic memory

Type of earwax

Learning from mistakes

Analysed genes Scientific sources

94 102

SUMMARY OF YOUR GENETIC RESULTS GENETIC RISK FOR CERTAIN DISEASES Alzheimerâ&#x20AC;&#x2122;s disease

Slightly decreased risk

Your risk for developing Alzheimer's disease is slightly decreased. Even though the disease remains incurable for the moment, you yourself can influence its course and mitigate symptoms with appropriate medication.

Asthma

Average risk

We have determined that you have an average risk of developing asthma. Asthma is primarily developed during childhood years. There are numerous preventive measures which could help reduce the probability of developing the disease.

Atrial fibrillation

Average risk

The results of your analysis show that you have an average genetic risk of developing atrial fibrillation. Nevertheless it is important to be aware of the fact that genetic influence is not the only factor for the development of the disease. There are other factors which can influence the development of atrial fibrillation.

Coeliac disease

Slightly decreased risk

Your risk of developing coeliac disease is slightly decreased in comparison to the rest of the population. However your genetic makeup is not the only factor in the development of the disease and does not immediately rule out its possible occurrence.

Glaucoma

Slightly increased risk

You have a slightly increased genetic risk of developing glaucoma compared to the rest of the population. You are advised to follow regular preventive measures.

Multiple sclerosis

Decreased risk

You have a decreased risk of developing multiple sclerosis. The disease is still incurable, but its development can be impeded with appropriate medications, a healthy diet and an active life style.

High blood pressure (Hypertension)

Average risk

Your genetic makeup determines an average risk for developing hypertension. For this reason we recommend that you closely follow preventive measures. A high blood pressure is no reason to worry, as the treatment of hypertension has a very high success rate.

Psoriasis

Increased risk

Your risk of developing psoriasis is increased, but your absolute risk is still low as in average population only 2.5 per cent of people are affected with psoriasis.

Rheumatoid arthritis

Decreased risk

Your genetic analysis has shown that you are carrier of the genetic variants which determine a decreased risk of developing rheumatoid arthritis.

Restless leg syndrome

Slightly increased risk

Your genes determine a slightly increased genetic risk of developing restless legs syndrome. Simple preventive measures are helpful if this syndrome should actually appear.

Diabetes mellitus type 1

Decreased risk

We have determined that you have a decreased genetic risk of developing diabetes mellitus type 1. The disease usually appears during childhood or adolescence. Adults have a very low risk of developing diabetes mellitus type 1.

Diabetes mellitus type 2

Average risk

You have an average genetic risk for developing diabetes mellitus type 2. You yourself can do a great deal to prevent its development and mitigate its consequences, and this is why we advise you to take into consideration the preventive measures.

Myocardial infarction (Heart attack)

Slightly increased risk

We have determined that you have a slightly increased genetic risk of suffering a heart attack in comparison to the rest of the population. By leading a healthy life you can significantly decrease this risk.

Venous thromboembolism

Slightly increased risk

The analysis of genes associated with the development of venous thromboembolism, showed that you are a carrier of less favourable gene variants, and thus have a slightly increased risk for venous thromboembolism.

Gallstones

Slightly decreased risk

The analysis of the ABCG8 gene sequence has shown that you have two common copies of the gene present. This genetic makeup is present in 80% of Caucasian people and determines a slightly decreased risk of developing gallstones.

SUMMARY OF YOUR GENETIC RESULTS GENETIC RISK FACTORS FOR DEVELOPING CANCER Skin cancer (Basal-cell carcinoma)

Increased risk

In comparison to the entire human population your genetic makeup determines an increased risk for developing basal-cell carcinoma. However, it is important to know that genetic influence is not the only risk factor.

Lung cancer

Increased risk

Your genetic makeup determines that you have an increased risk for developing lung cancer. Since smoking is a major risk factor for developing lung cancer, then due to your genetic makeup we additionally advise you to quit smoking in case you are a smoker.

Colorectal cancer

Slightly increased risk

We have determined that your genetic risk for developing colorectal cancer is slightly increased. Beside your genetic factors, some environmental factors are also important for the diseaseâ&#x20AC;&#x2122;s occurrence. We can use these environmental factors to our advantage and reduce the risk of developing the disease.

Breast cancer

Slightly decreased risk

The analysis has shown that you have a slightly decreased genetic risk of developing breast cancer. In spite of this we recommend regular and detailed self-examinations of the breasts after the age of 20 and immediate reporting of every suspicious change to your doctor.

Clopidogrel - prevention of blood clotting

Less efficient metabolism of clopidogrel

One of the two copies of your CYP2C19 gene encodes an inactive enzyme. This is why you are likely to need a replacement of clopidogrel therapy with alternative treatments.

Metformin - regulation of blood sugar

Average likelihood of metformin effectiveness

According to the result of your genetic analysis, you belong to a group of people for whom the therapy with metformin shows an average effectiveness.

Omeprazole - inhibition of gastric acid secretion

Effective function of omeprazole

You are the carrier of one normal and one rare copy of the CYP2C19 gene that encodes a less active enzyme. However, this has no effect on the metabolism of omeprazole, so therapy is recommended at a normal dosage.

Perindopril - treatment of stable coronary artery disease

Perindopril is an effective treatment

You are a carrier of the AT1 and BK1 gene combination, which determines that the therapy with perindopril will be successful.

Statins - lowering blood cholesterol

Normal likelihood for developing myopathy

You are the carrier of two normal copies of the SLCO1B1 gene, so for you it is completely safe to take medications from the statin group that contain active ingredients pravastatin, simvastatin or atorvastatin.

Warfarin - prevention of blood clotting

Lower starting dosage of warfarin

Due to the combination of your genes, you will need a lower starting dosage of warfarin.

MEDICAMENT RESPONSE

GENETICALLY DETERMINED PHYSICAL FEATURES AND TRAITS Eye colour

72% chance of blue eyes, 27% chance of green eyes, 1% chance of brown eyes

Sensitivity to pain

Average sensitivity to pain analysis has shown that you are a carrier of two common copies of the SCN9A gene, which

Muscle structure

Increased muscle endurance

Your genetic analysis has shown that you are a carrier of such ACTN3 and PPAR alpha gene sequences, which give you a predisposition to be more successful in sports where endurance is required, similar to long distance runners.

Nicotine addiction

Increased risk for addiction

Your risk for nicotine addiction is increased because you have two unfavourable copies of the CHRNA3 gene. About 15 percent of the population has such a genetic makeup.

Resistance to malaria (type Duffy)

You are not resistant to infection

The analysis of the DARC gene, which encodes for the Duffy antigen, reveals that you are the carrier of two common copies of the gene. This genetic makeup is associated with susceptibility to Plasmodium vivax and knowlesi infection, which would cause malaria.

Genetic analysis has shown that you are a carrier of two common copies of the gene HERC2. Most people of Caucasian origin have such genetic makeup, while it's actually completely absent in Asian and African populations. The SCN9A gene is associated with controlling the level of pain that an individual detects. Your determines that your perception of pain is normal.

SUMMARY OF YOUR GENETIC RESULTS GENETICALLY DETERMINED PHYSICAL FEATURES AND TRAITS Resistance to infection with noroviruses

You are not resistant to the infection

Your genetic analysis has shown that you are a carrier of one rare and one common copy of the FUT2 gene, which determines that you are not resistant to infection with noroviruses. About 50 percent of people in the Caucasian population have such genetic makeup.

Perception of bitter taste

More intense perception of bitter taste

Your genetic analysis has shown that you are a carrier of one common and one altered copy of the gene TAS2R38, which makes you more perceptive to certain bitter tastes.

Alcohol metabolism

Efficient alcohol metabolism

Your genetic makeup determines an efficient metabolism of alcohol. You are a carrier of the most favourable genetic makeup, and most probably do not have problems with alcohol metabolism and alcohol flush.

Caffeine metabolism

Slow caffeine metabolism

The analysis of your genetic makeup revealed one rare and one common copy of the gene CYP1A2, which determines slow caffeine metabolism. About 40 percent of Caucasians have such a genetic makeup and 48 percent of people metabolize caffeine as slowly as you.

Lactose metabolism

Ineffective metabolism

The analysis of your DNA has shown that you are a carrier of two unfavourable copies of the gene MCM6, which determines an extremely reduced amount or complete absence of the enzyme lactase and consequently results in lactose intolerance.

Episodic memory

Better episodic memory

You are a carrier of one common and one rare copy of the KIBRA gene, so you have better episodic memory compared to people who have two common copies of the gene. About 43 percent of the population has such a genetic makeup as you have.

Type of earwax

You have wet earwax type genetic makeup is most frequent in European population and determines that you have a wet

Learning from mistakes

More effective learning from mistakes

The genetic analysis has shown that you carry two common copies of the ABCC11 gene. This type of earwax.

Your analysis of the DRD2 gene, which affects the effectiveness of learning from mistakes, has shown that you carry two favourable copies of the gene, resulting in more effective learning from mistakes. About 65 percent of all people have such a genetic makeup.

Genetic testing facts People are almost identical to each other Like all living creatures on Earth, humans are also the result of evolutionary development that has been going on for millions of years. The hereditary material that determines our development and appearance is transmitted from generation to generation – that is why most people have two legs and hands, five toes on each limb, a lung and a heart. These are just some of the basic properties which are common to all of us as two separate individuals actually share as much as 99.9% of the same hereditary material. Statements like “like father, like son” are very much true as the genetic composition of an individual is a unique combination of the DNA material provided by both the mother and the father, and the numerous features and similarities of this composition are visible on the outside. Gregor Mendel discovered this as early as the 19th century, after having noted that biological differences are inherited from parent organisms as specific identifiable characteristics. For his research he used a pea plant, and demonstrated that the inheritance of certain traits of the plant follows particular patterns.

But we are still different …

Genetic composition determines much more than just the structure of a pea plant, or the colour of our eyes and hair, as it has a significant impact on the development of the entire body and it arranges our response to environmental stimuli. After a more detailed examination we find that we are in fact very different – some eat vast amounts of food and never gain weight,

others are exceptionally talented in certain sports, while others still drink a cup of coffee and spend a sleepless night. These and many other individual traits are largely a consequence of the differences within the remaining 0.1% of our hereditary notation.

Every cell contains DNA organized in chromosomes People are unique creatures. We consist of a hundred and thousand billion cells. Within each of them there is the DNA double helix carrying information for creating an organism. In each cell there are two copies of DNA: one from the father and the other from the mother. Each copy of DNA is arranged in super-bend structures, called chromosomes. In each cell we have 23 pairs of chromosomes. Exceptions are the gametes (eggs and semen) where we have only one copy of DNA; meaning only 23 chromosomes.

DNA is formed from a sequence of four different nucleotides

Genes carry the information for the creation of proteins

The DNA molecule is composed of approximately three billion nucleotides. Each nucleotide consists of a phosphate group, pentose (monosaccharide with five carbon atoms) and a nitrogenous base. The individual nucleotides differ only in their nitrogenous bases. The human DNA contains four different nitrogenous bases and therefore four different nucleotides: cytosine (C), guanine (G), thymine (T) and adenine (A).

Proteins are the foundation of the body. Also all the enzymes, the biological molecules which are the key to the proper operation of our organism are proteins by nature. Proteins are built from smaller molecules, named amino acids. Genes actually carry the information which tells the amino acids how to create the corresponding sequence. The different amino acids in a specific sequence give rise to the corresponding protein.

The specific sequence nucleotides creates a gene

Imagine an incredibly long helix (three billion nucleotides) in which the sequence of the letters C, G, T, A is fixed. The individual sectors of this incredibly long helix (parts of the specific sequence of the letters C, G, T and A) carry the information for the creation of protein and consequently create genes. There are over 25 000 of these sectors, meaning that this is the precise number of genes we have.

SNPs makes us unique Mutation in Latin means change. When we refer to mutation in genetics, we mean the change in the DNA sequence. This can occur in various ways: a nucleotide can be inserted into a sequence, another can be erased, and another still can be replaced by another one. The replacement of one nucleotide by another, which is then inherited by the descendants and kept within the population, is called the SNP. SNPs can cause a protein, encoded by a gene, to change, which means that its function will be changed as well. And even though people are identical in more the 99% of their hereditary notation, the SNPs (and some rare DNA mistakes) make everyone unique.

The SNPs are inherited from parents and determine the genotype Sex cells, as opposed to body cells, contain only 23 chromosomes. Each parent gives their child 23 chromosomes, which means that the human body contains

Genetics and genetic analysis 46 chromosomes; therefore each of our body cells has two copies of a gene for each characteristic. When the gene copies are identical, they are referred to as homozygous, and when the copies are different, the person is a heterozygote. This gene state (homozygous or heterozygous) is the genotype. The gene copies are different when the nucleotide sequence differs in at least one site. For instance, a gene copy contains the A nucleotide in a specific location, while the other copy has the G nucleotide in the same place. We say that this person has two different alleles in the same location.

The genotype phenotype

influences

the

The two gene copies influence the final characteristic, the phenotype, together. This can be clearly seen when we inherit lightly tanned skin from one of the parents, and a darker tone from the other, which makes our skin tone somewhere in between. Both body height and weight are also an evident example. The phenotype is the visible characteristic of an individual, like the above mentioned skin coloration or hair colour, or any other characteristic, like the caffeine metabolism, the predisposition to higher blood pressure or effectiveness of therapy with certain medications.

The importance of association studies 12

Numerous diseases are influenced by several genes as every gene somewhat contributes to the final risk. The SNP itself does not cause disease; it is only the change in a

specific location of the DNA that is related to the risk. The SNP is discovered with the help of association studies in which we compare the genetic composition of people suffering from certain diseases with that of people who are healthy. If we find that certain SNPs are more frequent among people suffering from certain diseases, we can conclude that these SNPs are related to the development of said diseases.

Does genetic analysis tell the absolute truth? With the analysis of SNPs we can calculate the probability of development of a certain disease usually compared to the average risk within the population. Despite the fact that this is a probability backed with a statistic foundation within scientific research, knowing the SNPs cannot predict with certainty whether an individual will develop particular conditions or not. Various environmental factors can influence the development of disease, as well as possible unexplained genetic factors.

Applicability of the genetic analysis Genetic analysis is not a crystal ball that predicts the future. It is a scientifically-based starting point for calculating the genetic burden, which shows us the level of probability of developing disease due to our genetic composition. Taking into consideration the fact that both genes and the environment affect us, information of this kind can help us reduce the risk of disease. It encourages us to immediately change the way we live our life (e.g. quit smoking) either by aiding the early discovery of disease through early preventive examinations (e.g. lumps in the case of breast cancer, and enlarged prostate in the case of prostate cancer) or by effectively curing the disease. The genetic analysis allows us to fairly accurately predict our response to the therapy with some important medications. Based on the results of your genetic analysis, your physician can adjust the dosage of certain medications accordingly or he can replace the primary medication with an alternative one, which can either prevent side effects (health consequences) or improve the effectiveness of therapy. A genetic analysis in addition to providing information about genetically determined disease susceptibility and medicament response offers additional insights. For example, with the help of the genetic analysis we can determine the individualâ&#x20AC;&#x2122;s response to lactose, alcohol and caffeine, as well as learn about other personal traits and talent, which were not known until now.

Interesting genetic facts • Two individuals share as much as 99.9% of the same genetic material and differ in only 0.1% of it. • Genetic similarity - People share 7% of genetic material with the E. coli bacteria, 21% with worms, 90% with mice and 98% with chimpanzees. • If you were to recite the entire ATCG sequence, pronouncing each of its 3 billion letters the genetic material notation is made of at a rate of 100 ATCG sequences per minute without sleeping, eating or drinking, you would cite for 57 years. • If all 46 chromosomes were combined and arranged lengthwise, the total length would be 1.8 meters. If all the chromosomes from all the nuclei in the human body (1014 cells) were to be arranged lengthwise, it would measure around 180 000 million kilometres. For a better understanding, compare it to the distance from the Earth to the Sun which measures 150 million kilometres. The length of the DNA would thus be one thousand times greater. • A dot at the end of a sentence is the size of a thousands of cell nuclei. • In the case of autosomal recessive hereditary diseases, the recessive gene, situated on an autosomal chromosome, is passed on in the family. If a person has only one copy of this gene, he is its carrier without being aware of it, as the disease has not developed. • Haemophilia is a recessive disease and linked to the sex chromosome X. Women have two X chromosomes. That is why only individuals carrying two recessive genes develop the disease. The women who carry only one recessive gene are the transmitters of the disease. All men with the recessive gene will develop the disease as they only have one X chromosome. These facts were well known with the Jewish population, as the sons of the women who were considered to be transmitters of the disease were exempt from circumcision. • Beside the DNA present in the nucleus, people also have DNA present in mitochondria. This DNA is only inherited from the mother and it is used in studies related to female ancestry. An interesting fact noticed in bees is that their mitochondrial DNA can also be inherited from the father.

• On average, one out of 180 children is born with a chromosomal abnormality. The result of the mot frequent abnormality is Down’s syndrome.

• Only 2 percent of the human genome contains information regarding the formation of proteins. All the rest are so called non-coding regions. • In a typical group of 50 African monkeys, there are more genetic variations than in the entire human race. This means that the entire human race is the descendant of a small group of people from prehistoric times. This scientific phenomenon is also referred to as a »bottleneck«. The phenomenon is probably the consequence/result of unfavourable weather conditions which lead to the death of most of the prehistoric people. The entire human race developed from a small group of survivors.

Human being

Hen

Drosophila melanogaster (wine fly)

Butterfly

Corn

Rice

Number of chromosomes

Around 380

Number of genes (approx)

25.000

23.000

14.000

Unknown

59.000

50.000

Length of genome (million base pairs)

3.300

1000

165

124.900

2.500

441

Species

How to use the genetic guidebook The basic purpose of the Personal genetic analysis is to allow a person to access the secrets of his/ her genetic makeup and to introduce the latest scientific discoveries in an easy-to-understand and useful way. We can influence the environmental factors which affect our day-to-day life by knowing our genetic potentials and predispositions and can regulate the activities which allow us to develop our potential in more effective way or to avoid certain inconveniences. To better understand the contents of your Personal genetic analysis please read the genetic guide instructions carefully. Goal of each analysis is to familiarize individual with a particular field in a clear and intuitive way. Each analysis contains a general description, preventive measures, a genetic result and an individualised medical advice. Personal genetic analysis is thematically divided into four sections, which are differently coloured in order to achieve a greater transparency. Each section contains a table of contents, followed by individual analyses, which consist of a general description of certain analysis, the results of genetic analysis, preventive measures and appropriate health advice. The results are presented in different colours to make it easier for you to notice which analyses you should pay more attention to: â&#x20AC;˘

Green denotes a decreased risk; a favourable result

â&#x20AC;˘

Orange denotes an average risk; an average result

â&#x20AC;˘

Red denotes an increased risk; an unfavourable result

The coloured results serve only as first information. Further details about the genetic analysis are presented with graphs and detailed textual descriptions.

Displaying the results for drugs and traits Drugs and traits section is divided into two parts:

Metformin - regulation of blood sugar Your result Decreased likelihood of metformin effectiveness According to the result of your genetic analysis, you belong to a group of people who are slightly less likely to benefit from therapy with metformin.

You are a carrier of such an allelic combination of the SLC22A1 and C11ORF65 genes, which denotes a slightly lower efficiency of metformin for the treatment of diabetes type 2. Studies have shown that in people with your genotype, a reduction of the glycated haemoglobin levels (a sign of successful therapy) was not immediately detectable after the beginning of the treatment. This does not mean that metformin has no effect whatsoever. It just means that successful therapy is slightly less likely. We encourage you to inform your doctor of the possibility of lower effectiveness of metformin therapy due to genetic reasons. You can be prescribed with any additional drugs on the basis of additional analyses.

Tradenames of drugs Metformin: • • • • • • • •

AGLURAB AVANDAMET EUCREAS GLUCOPHAGE GLUCOVANCE METFOGAMMA METFORMIN AUROBINDO SIOFOR

The field without colour contains some general information about a particular drug or trait and some additional information describing the content in detail.

Metformin is a medication that is primarily meant for regulating the blood glucose levels. However, the administration of the drug also results in a lower LDL cholesterol and triglyceride levels. Metformin is mainly taken for the treatment of diabetes type 2, usually as monotherapy or in a combination with other drugs. Efficacy of metformin is analysed by measuring the glucose levels in the blood or by determining the presence of glycated haemoglobin (HbA1c), the amount of which should not be higher than 7 per cent, otherwise the use of metformin is considered to be ineffective. Although metformin is the first treatment of choice for diabetes type 2, its effectiveness greatly varies between individuals. The most important factors that influence the effectiveness of metformin are the SLC22A1 and C11ORF65 genes.

The mechanism of metformin activity Metformin works mainly in two basic ways: by improving the sensitivity of the organism to insulin and by inhibiting the glucose production in the liver. Hepatic synthesis of glucose takes place three times faster in people suffering from diabetes type 2 than in healthy organisms. This is due to the inefficient activity of the enzyme AMPactivated protein kinase (AMPK), which plays an important role in the regulation of insulin activity and energy balance of the whole body, and also participates in the metabolism of glucose and fat. Metformin affects the activity of the enzyme AMPK in order to reduce the glucose production by one-third, resulting in a low blood glucose level. Metformin lowers the level of glucose in the blood through other mechanisms: by slowing down the absorption of glucose from the intestine into the blood, by increasing glucose uptake in the muscle cells, by reducing its absorption in the digestive tract and by increasing the oxidation of fatty acids. The efficacy of metformin is primarily affected by polymorphisms in two genes. The SLC22A1 gene encodes the trans-membrane transporter 1 (OCT1) important for the transport of metformin to the cells and outside of the cells, while the other polymorphism is located in the C11ORF65 gene. This gene regulates the activity of the ATM gene, which is responsible for the phosphorylation and the activation of the AMPK enzyme.

“Your result” includes the presentation of the results in colour and a brief description. The following medical advice explains in detail the link between your genetic makeup and response to a certain drug, and directs you accordingly. Recommendations include practical measures and guidelines for appropriate action, leading to better health and wellbeing. 71

The titles of medicaments state the pharmaceutical subsbstance that is used for treatment. For an easier understanding, in the analyses related to medicaments, drug tredenames are given in a separate box.

Displaying results for diseases The disease section is divided into 3 parts:

Asthma

The upper left column contains basic information about the disease and introduces you to the general disease thematic, as well as to other important information regarding the disease symptoms and consequences.

There are various autoimmune diseases which affect the respiratory system by narrowing the airways. Amongst them, asthma is the most common. The airways of asthma patients are extremely sensitive and some situations can lead to inflammatory reactions which in turn lead to the narrowing of airways and the swelling of the airway mucosa and consequently to an additional reduction of the airway’s diameter. This leads to the feeling of suffocating and other significant symptoms of asthma. Asthma is classified as either atopic (extrinsic) or non-atopic (intrinsic). The cause for intrinsic asthma is unknown while extrinsic asthma is provoked by specific allergens. The most important factor for the development of extrinsic asthma is the presence of atopy (atopic syndrome) – allergic hypersensitivity reactions (in most cases it is inherited).

Coloured result with a short description.

“Your risk” shows your lifetime risk which takes into account your genetic factors and your race. Lifetime risk tells on average how many people with the same genetic makeup as you have, will develop the disease during their lifetime.

Asthma is present in 5 % of world’s population according to the World Health Organisation data Asthma can appear at any age, however in most cases it appears before the age of 10. We distinguish two types of asthma: atopic, caused by known allergens, and non-atopic, the cause of which is still unknown. When the patient inhales an allergen, special immune cells called mastocytes under the influence of IgE antibodies begin to secrete numerous inflammatory mediators (histamine being the most important of them). This leads to an inflammatory reaction – the swelling of the airway mucosa and the narrowing of the airways. A diagnosis is made on the basis of a clinical examination and the testing of pulmonary function. Asthma can also be confirmed by measuring the response of the airways to the presence of special substances.

Asthma is manifested in attacks during which the patient has trouble breathing. These attacks can be triggered by physical activity, and in women the disease worsens before menstruation. The attack’s intensity depends on the possible presence of an infection in the airways, specific allergens and air temperature. Attacks can also be caused by certain medications, mostly aspirin. Other factors responsible for the development of the disease are air pollution, health issues in the workplace, infections and emotional stress.

“The risk of the population” –shows the risk of the “typical” individual within a population of the same demographic group. It gives you the percentage of all people who develop certain disease during their lifetimes regardless of their genetic makeup.

Your result Slightly decreased risk

Your risk

6,65 %

Population risk

13,00 %

Genes vs Environment

Genes

60%

Environment

40%

The middle section, positioned under “Your result” is intended for the result of your genetic analysis.

Prevention and therapy

Medical advice We have determined that you have a decreased risk of developing asthma. Asthma is primarily developed during childhood years. There are numerous preventive measures which could help reduce the probability of developing the disease. It is of the utmost importance that asthma patients avoid polluted air and that they quit smoking. Excessive physical activity, as well as emotional stress, is also detrimental. Flue vaccination and avoidance of any respiratory infections are also highly recommended. Relaxation techniques, such as autogenous training and yoga can have very positive influence on asthma patients. If you are sensitive to a certain allergen then you should try to avoid it. If you are allergic to common dust then you should remove all rugs and pillows where dust mites might gather. You should try to use up-to-date vacuum cleaners which do not cause the raising of dust. If the allergens are natural, such as pollen, then there are special filters you can use during the pollen season. These filters circulate the air flow and hold off the allergens.

Preventive measures in the case of asthma, are mainly directed to avoidance of known allergens, smoking, polluted air, dust, stress and excessive physical activity.

The column on the far right presents therapeutic and preventive measures, by which we can influence the development and progress of the disease. The preventive recommendations are assembled by doctors and other experts in the relevant fields and they represent the measures, by which we can decrease the risk of certain disease.

The recognition and avoidance of allergens causing asthmatic reactions are the most important preventive measures for asthma patients, as they reduce the frequency of the attacks. This is especially important with prevention of the development of intrinsic asthma which develops with periodic exposure to the same allergen. Asthma patients have at their disposal two groups of medications which are classified according to their purpose: Short-acting medications, or bronchodilators, are used for those asthma attacks in which the first signs of breathing problems appear. They expand the airways by relaxing the muscles. The group of medications includes beta-2-agonists, such as salbutamol and they are mostly inhalers, however they can also be found in the form of injections. The other group is so called medications for long-term control and they must be used daily. They are anti-inflammatory medications (such as corticosteroids), which can be found in the form of inhalers. They are usually the initial choice for every treatment. Systemic antihistamines can also be used. They are used for mitigating hypersensitivity symptoms on mites, cat hair, and pollen. People who are hypersensitive to a known allergen can also be treated with immunotherapy, where the allergen is periodically injected under the skin in order to adapt the afflicted person’s immune system to it. In the first 30 weeks of the therapy the patient receives the injection once or more times a week. In time, the dosages are spread out more until they are given about once a month. The therapy lasts from 3 to 5 years; in certain cases it can last longer.

The “Medical advice” section is constructed on the basis of your genetic analysis result and it contains recommendations, which you should take into consideration. We advise you to follow them, as appropriate preventive measures are crucial for lowering the risk of disease.

“The influence of the environment and genetics” is a measure that we use to determine how much our genes influence the development of a certain disease. The greater the heritability is, the greater influence our genes have, and the smaller influence the environment has. However, completely all the diseases leave us some part to be influenced by environmental factors (eating habits, physical activity, the presence of stress, smoking, alcohol, etc.), which means, by taking into account preventive measures and medical advice, we can do a lot to prevent diseases.

Genetic risk for certain diseases

he entire plan of our organism is written in the genes. They are the ones who decide the function and structure of our body. If we have inherited

an important error in our genetic composition, we will develop a certain genetic disease. Nowadays it is the responsibility of doctors to discover an error of this kind. Genes carry information regarding our tendency to develop numerous diseases. Genetic and environmental factors are also important in the development of certain diseases. This is why we alone can greatly contribute to their development. With the help of our information you can change your lifestyle and prevent the development of the disease to which you are most exposed. When this is not possible, you can detect the disease with timely examinations while the treatment is still successful.

List of analyses Alzheimerâ&#x20AC;&#x2122;s disease Asthma Atrial fibrillation Coeliac disease Glaucoma Multiple sclerosis High blood pressure (Hypertension) Psoriasis Rheumatoid arthritis Restless leg syndrome Diabetes mellitus type 1 Diabetes mellitus type 2 Myocardial infarction (Heart attack) Venous thromboembolism Gallstones

Alzheimer’s disease Alzheimer’s disease is type of dementia which is related to the progressive diminution of mental capacity. There are several different types of dementia and amongst them Alzheimer’s disease is the most frequent. It is an age related disease, as it affects 5 % of people by the age of 65 and 20 % by the age of 80. The disease starts with the inability to recall recent events. Interestingly, the patient has no trouble recalling the events from the more distant past. Later on, as the disease progresses, other problems appear, such as: difficulties while speaking, loss of people recognition skills, impaired hand-eye coordination, spatial orientation and difficulties with solving abstract problems. In its late phase, hallucinations, delusions and personality changes may appear.

Your result Slightly decreased risk

Your risk

14,63 %

Population risk

18,50 %

Numerous genes are significantly involved in the development of the disease Despite the fact that the cause of disease in most cases remains unknown, there are, however, some rare families, where gene mutations directly responsible for the development of this disease, have been discovered. These genes are PSEN1, PSEN2 and APP and they play a key role in the development of the central nervous system. In most people, the development of the disease cannot be explained only with the state of one gene, but with mutual functions of numerous genes, which are usually responsible for the changes in the genetic composition. One of the most important genes of this kind is APOE4. It is known that a specific change in the sequence of this gene determines the higher risk for developing Alzheimer’s disease, even though the precise physiological role of this change remains to be elucidated.

If the patient’s brain tissue is examined under a microscope, protein threads (neurofibrillary tangles) are visible in his nerve cells. Protein accumulations (neuritic plaques) are dispersed between the nerve cells, which is not noticeable in healthy tissue. These changes are more explicit in the brain’s temporal lobe, the area important for memory formation. Simultaneously the brain develops a deficiency of different chemical transmitters important for the communication between individual nerve cells. These are called neurotransmitters. By the transmission and reception of neurotransmitters, brain cells communicate between themselves and in this way transfer information. In case of Alzheimer’s disease, the nerve cells, which communicate by excreting the neurotransmitter acetylcholine, are most affected.

Genes vs Environment

Genes

70%

Environment

30%

Prevention and therapy

Medical advice Your risk for developing Alzheimer's disease is slightly decreased. Even though the disease remains incurable for the moment, you yourself can influence its course and mitigate symptoms with appropriate medication. Your results show that you have a slightly decreased risk for developing Alzheimer's disease. Due to longer life expectancy in humans, the disease's frequency increases each day. The disease is becoming more frequent on a daily basis. The disease cannot be prevented or cured, but it is important to know that at least 200 medications for the treatment of Alzheimer's disease are currently in the last phase of clinical trials worldwide. In any case, we recommend that you maintain a good physical condition, play sports or find a hobby, perform intellectual and memory games (chess, learning new languages, solving crosswords). All this could help to slow the progression of the disease. The maintenance of social contacts is also

Experts recommend intellectual activity such as chess, learning new languages, solving crosswords and mostly regular social contact with family and friends. The brain is like a muscle which means that if it is not frequently exercised its efficiency will diminish with time. Intellectual activity may slow the progression of Alzheimer’s disease and mitigate its course. Moderate physical activity and playing sports is also recommended. Dance is especially useful, as it demands learning of new movements, memorizing dance steps and enables stretching of the body and its relaxation. The brain of Alzheimer’s disease patients often shows signs of a smaller stroke and this is why it is important that the patients lead a healthy life, mostly by maintaining of regular blood pressure and low LDL cholesterol and also quit smoking. These are some of the ways patients can improve their overall health state. The treatment of potential cardiac dysrhythmia is highly recommended, as it is one of the risk factors for a stroke. Effective prevention of Alzheimer’s disease with medications is still unknown In the past a vaccine was used which was believed to help to improve the state of the brain of patients with Alzheimer’s. Unfortunately, this vaccine was unsuccessful. The research had to be prematurely stopped due to numerous patients developing encephalitis and succumbing to it. At the moment, intensive research for the development of newer and cleaner vaccines is being conducted and we hope to find a way of improving the treatment options in the future.

Asthma There are various autoimmune diseases which affect the respiratory system by narrowing the airways. Amongst them, asthma is the most common. The airways of asthma patients are extremely sensitive and some situations can lead to inflammatory reactions which in turn lead to the narrowing of airways and the swelling of the airway mucosa and consequently to an additional reduction of the airway’s diameter. This leads to the feeling of suffocating and other significant symptoms of asthma. Asthma is classified as either atopic (extrinsic) or non-atopic (intrinsic). The cause for intrinsic asthma is unknown while extrinsic asthma is provoked by specific allergens. The most important factor for the development of extrinsic asthma is the presence of atopy (atopic syndrome) – allergic hypersensitivity reactions (in most cases it is inherited).

Your result Average risk

Your risk

12,51 %

Population risk

13,00 %

Genes vs Environment

Genes

60%

Environment

40%

Prevention and therapy

Medical advice We have determined that you have an average risk of developing asthma. Asthma is primarily developed during childhood years. There are numerous preventive measures which could help reduce the probability of developing the disease. It is of the utmost importance that asthma patients avoid polluted air and that they quit smoking. Excessive physical activity, as well as emotional stress, is also detrimental. Flu vaccination and avoidance of any respiratory infections are also highly recommended. Relaxation techniques, such as autogenous training and yoga can have very positive influence on asthma patients. If you are sensitive to a certain allergen then you should try to avoid it. If you are allergic to common dust then you should remove all rugs and pillows where dust mites might gather. You should try to use up-to-date vacuum cleaners which do not cause the raising of dust. If the allergens are natural, such as pollen, then there are special filters you can use during the pollen season. These filters circulate the air flow and hold off the allergens.

Preventive measures in the case of asthma, are mainly directed to avoidance of known allergens, smoking, polluted air, dust, stress and excessive physical activity. The recognition and avoidance of allergens causing asthmatic reactions are the most important preventive measures for asthma patients, as they reduce the frequency of the attacks. This is especially important with prevention of the development of intrinsic asthma which develops with periodic exposure to the same allergen. Asthma patients have at their disposal two groups of medications which are classified according to their purpose: Short-acting medications, or bronchodilators, are used for those asthma attacks in which the first signs of breathing problems appear. They expand the airways by relaxing the muscles. The group of medications includes beta-2-agonists, such as salbutamol and they are mostly inhalers, however they can also be found in the form of injections. The other group is so called medications for long-term control and they must be used daily. They are anti-inflammatory medications (such as corticosteroids), which can be found in the form of inhalers. They are usually the initial choice for every treatment. Systemic antihistamines can also be used. They are used for mitigating hypersensitivity symptoms on mites, cat hair, and pollen. People who are hypersensitive to a known allergen can also be treated with immunotherapy, where the allergen is periodically injected under the skin in order to adapt the afflicted personâ&#x20AC;&#x2122;s immune system to it. In the first 30 weeks of the therapy the patient receives the injection once or more times a week. In time, the dosages are spread out more until they are given about once a month. The therapy lasts from 3 to 5 years; in certain cases it can last longer.

Atrial fibrillation Atrial fibrillation is a disorder in which the patient can develop an irregular heart beat rhythm, known as dysrhythmia. With a normal heart beat, electric impulses travel from the sinoatrial node, which regulates the heart rate, through the conductive fibres to the atrioventricular node and later through the conductive fibres of the ventricles. In atrial fibrillation these electric impulses do not travel their natural path but chaotically spread to all directions. The consequence of a disorderly behaviour of the electric impulses is an irregularity in the heart muscleâ&#x20AC;&#x2122;s movements, or fibrillation. An irregular or fast heart beat, where the atrial rate reaches up to 175 times a minute, is characteristic of fibrillation. 0.5 % of the population of Europe and USA suffer from atrial fibrillation, and the development of the disease is more frequent at an advanced age. The disease can develop in all races, and it affects both men and women equally.

There are numerous risk factors which can cause atrial fibrillation

Your result Average risk

Your risk

24,08 %

Population risk

25,00 %

Among the risk factors are a high blood pressure, heart attacks, valvular heart disease, congenital heart disease, metabolic disorder (thyroid disease), exposure to alcohol and drugs, infections and postoperative states (heart surgery). The causes for atrial fibrillation are mostly the irregular structure of cardiovascular system or heart damage. Low blood pressure (hypotension) occurs when the heart pumps less blood than normally due to its irregular rhythm. Beside hypotension symptoms of the disease also include palpitations (a feeling of an unnaturally fast heart beat), weakness, shortness of breath, confusion and chest pains.

Atrial fibrillation can cause heart failure as an irregularly working heart cannot ensure the blood flow needed for the normal functioning of the entire organism. Atrial fibrillation can also cause a stroke. Because of the abnormal functioning of the atriums the blood does not flow evenly and starts to stall and coagulate. These clots can travel through the blood circulation and cause the occlusion of the blood vessels in other organs. There is nothing more dangerous than a blood clot finding its way to the brainâ&#x20AC;&#x2122;s blood vessels, as this can cause a stroke.

Genes vs Environment

Genes

60%

Environment

40%

Prevention and therapy

Medical advice The results of your analysis show that you have an average genetic risk of developing atrial fibrillation. Nevertheless it is important to be aware of the fact that genetic influence is not the only factor for the development of the disease. There are other factors which can influence the development of atrial fibrillation. With the help of the genetic analysis we have determined that you have an average risk of developing atrial fibrillation. This does not mean that atrial fibrillation will definitely occur, or that it will definitely not, as there are factors, other than your genetic makeup, which can influence the development of the disease. Your risk depends also on other factors, such as the potential use of stimulants, the presence of a cardiovascular disease or a thyroid disorder, all of which increase the risk. A healthy life style (regular physical activity, appropriate eating habits, the maintenance of a normal body weight) and prevention or treatment of these conditions can substantially lower the risk

The timely discovery of an overworked thyroid, a cardiovascular disease, or a heightened blood pressure is essential for the prevention of atrial fibrillation. Alongside the abovementioned conditions, atrial fibrillation can be prevented with appropriate eating habits, healthy life style and regular physical activity, maintenance of a normal body weight and with appropriate medication. An excessive indulgence in alcohol and coffee is not recommended. The therapy has two main goals: • establishing normal heart rate, i.e. heart frequency control • prevention of blood clots The treatment is individually adjusted according to the seriousness of the symptoms, such as difficulty with breathing, dizziness, fatigue, chest pains and a pounding heartbeat. It is necessary to treat other medical issues which might be the cause of atrial fibrillation, like cardiovascular diseases and thyroid disorders. Patients suffering from atrial fibrillation are treated with a procedure named cardioversion. With this treatment an attempt is made to change the beating of the atriums from chaotic to normal. This is achieved with: • Medications (antiarrhythmics), required to be taken even after the initial treatment in order to keep a normal heart rate. • Electric shocks, which stop the heart for a short period of time, theoretically causing it to start functioning at a normal rate. This procedure is done with the use of anaesthetics. The conversion to normal sinus rhythm is sometimes unsuccessful. In this case the goal of the therapy is the maintenance of the heart frequency between 60 and 100 beats per minute, as a heightened heart frequency, which is connected to atrial fibrillation, is harmful to the heart in the long run. This can be done with the use of different medications, such as beta-blockers, digoxin and calcium channel blockers.

Coeliac disease Coeliac disease is an autoimmune disorder of the small intestine, a consequence of hypersensitivity to gluten – a protein found in numerous grains, mostly in wheat, rye and barley. The symptoms of the disease include a long lasting diarrhoea and bloating, manifesting as poor food absorption and a short stature. Coeliac disease most often occurs as early as childhood, but it can also develop in adulthood, in the latter case causing intestinal complications and numerous other medical troubles. When people suffering from coeliac disease ingest gluten, then their bowels have an immunological reaction, leading to the inflammation of the intestinal mucosa, the consequence of which is long lasting diarrhoea. There is an estimated 2 % of the population of Europe and of USA suffering from coeliac disease, which makes it one of the most common inflammatory diseases.

Your result Slightly decreased risk

Your risk

0,60 %

Population risk

0,90 %

An appropriate treatment combined with an adapted diet is of key importance It is of the utmost importance that coeliac disease is recognized and treated on time, as the frequent diarrhoea causes a lack of vitamins, which can have numerous consequences. The body’s immunity decreases and we are more exposed to osteoporosis. Coeliac disease can also be manifested in the inflammation of joints, tooth decay or the inflammation of skin. It has been proved that boys and girls suffering from an untreated coeliac disease reach puberty later, which can then lead to infertility, irregular menses and spontaneous abortions.

The disease can be diagnosed on the bases of a biopsy of the intestinal mucosa. Immunological examinations are important as well, as with them we can determine the presence of characteristic antibodies in the blood. Newer diagnostic criteria also include the usage of genetic tests, mostly the determination of the presence of the genetic notation for HLA-DQA1. HLA is an abbreviation for “human leukocyte antigen” the genes of which are located on the human chromosome number 6. The presence of these alleles does not immediately indicate coeliac disease, but the lack of them definitely denotes that the disease is non-existent. Patients who are treated for coeliac disease but do not have the HLA-DQA1 notation are extremely rare.

Genes vs Environment

Genes

70%

Environment

30%

Prevention and therapy Coeliac disease cannot be prevented, but, if it does develop, then its symptoms can be successfully countered with a gluten free diet.

Medical advice Your risk of developing coeliac disease is slightly decreased in comparison to the rest of the population. However your genetic makeup is not the only factor in the development of the disease and does not immediately rule out its possible occurrence. The analysis has shown that your risk of developing coeliac disease is slightly decreased in comparison to the entire human population. The disease affects 1 person out of 100 to 200 people on average. The disease cannot be prevented or cured. However, its symptoms can be successfully countered with a strict gluten-free diet. This is an autoimmune disease which is based on genetic exposure. Your risk of developing the disease is slightly lower; however it is still possible that the disease will occur. If you notice long lasting gastrointestinal symptoms, mostly diarrhoea and bloating, then there is a possibility that you suffer from coeliac disease. In this case, we recommend that you consult your doctor and try a gluten-free

A gluten-free diet allows the mucosa and the villi of the small intestine to recover. The organism then absorbs and uses nutrients which help the body to regain the lost weight. People suffering from coeliac disease should not consume products made of wheat, rye, barley and oats, wheat flour, grits, bread and bread crumbs, biscuits, pasta, soups, cakes and other similar food. Therefore, patients must be very cautious with the ingredients of numerous products, as they can easily contain additives of wheat origin (various emulsifiers, stabilizers and preservatives). The food label should contain information about the exact ingredients of the product. The products containing the following ingredients are appropriate for people suffering from coeliac disease: rice, corn, millet, buckwheat, soybeans, peas, beans, potatoes, chestnuts, lentils, chick peas, manioc, quinoa and amaranth. Vegetables, fruit, milk, eggs, meat, fish, honey, sugar and vegetable oils are also gluten-free. Despite the strict regulation of the European Union regarding the labelling of the possible presence of gluten, in some products there is a possibility of gluten contamination during the manufacturing process (dried meat products, soy sauces, sweets, icecream, meat products and other processed food). So if the absence of gluten cannot be determined with certainty, then these products are not recommended for people suffering from coeliac disease. There are numerous gluten-free products at your disposal and they are specially marked. They can be bought in the diet section of almost any grocery store. Some of them can also be found in pharmacies. Patients can easily identify gluten-free products by the crossed-out ear of wheat, a logo which ensures the absence of gluten.

Glaucoma Eyes are one of the most important parts of the body and we all want them to stay healthy until our old age. Nevertheless, a large number of diseases affect our eyes, among which is also glaucoma. Glaucoma represents a large group of diseases for which damage to the optic nerve occurs due to decay or deterioration of nerve fibers. It is also referred to as a secret thief of vision, because in its early stages it does not cause any pain and is inconspicuous. Glaucoma is one of the leading causes of blindness in the United States and elsewhere in the world. Statistics show that it is present in 12 percent of all persons with irreversible blindness. Weakened vision is detected only after the disease has progressed and due to this it is important to regularly measure the intraocular pressure by ophthalmologists.

Your result Slightly increased risk

Your risk

5,87 %

Population risk

4,00 %

The main risk factor for developing glaucoma is elevated intraocular pressure Intraocular pressure ensures a constant shape of the eyeball, which is made of a gelatine substance. In fact, the eye fluid, known as aqueous water, is holding the pressure on the eye. More precisely, eye fluid keeps the pressure especially in the eye lens, iris and cornea. Its task is to supply nutrients to the eye. The eye fluid is usually regularly secreted to the vascular system, problems however occur, when the fluid starts to accumulate in the eye. Then the intraocular pressure is raised, causing damage to the eyeball or nerve cells in the retina. This leads to progressive deterioration and potential loss of vision. Also sensitivity of the optic nerve is increased with glaucoma, an unbalanced blood flow to the eye, autoimmune reactions, diabetes and other physiological disorders can occur. The main symptom of glaucoma is deterioration of vision or field of vision. Vision becomes darker and more and more blurred. Unfortunately, patients experience this rather late, because the vision starts to deteriorate in the peripheral parts of the visual field. It is therefore very important to detect glaucoma early on, enabling measures to stop or slow down the development of the disease.

Primary glaucoma affects most often elderly people (over 65 years), short-sighted people with diopter greater than minus 4, patients with cardiovascular disease who have poor blood circulation in the body and, consequently, poor blood flow to the eye and to the optic nerve. Those with the disease present in a narrow family circle have a four times higher risk for developing glaucoma.

Genes vs Environment

Genes

15%

Environment

85%

Prevention and therapy Prevention is primarily aimed at the early detection of glaucoma with preventive eye tests after age 40 in every 2 years.

Medical advice You have a slightly increased genetic risk of developing glaucoma compared to the rest of the population. You are advised to follow regular preventive measures.

Due to the unfavourable genetic makeup it is important to regularly follow preventive measures that are primarily focused on the early detection of glaucoma with preventive eye tests after age 40 in every 2 years. If the specialist identifies an increase in intraocular pressure, then the prevention of the development and treatment of glaucoma focuses on lowering intraocular pressure. Treatment begins with eye drops that reduce intraocular pressure to a value at which we expect the glaucoma damage to stay stable. If drug therapy fails, then surgical and laser procedures are used to treat glaucoma.

Consistent treatment of elevated intraocular pressure is also important. Maintaining normal intraocular pressure with drugs slows down or inhibits the progression of the disease for the majority of patients. The diagnosis of this disease requires measuring the intraocular pressure, a visual field examination, and an ophthalmoscopic examination of the eye. The presence of characteristic changes in the optic nerve and loss of vision confirms the presence of glaucoma. Modern diagnostic methods such as imaging of the retina, allow very early detection of glaucoma and early initiation of treatment. Treatment of glaucoma focuses on lowering intraocular pressure. Treatment begins with eye drops that reduce intraocular pressure to a value at which we expect the glaucoma damage to stay stable. The level of the target pressure for an individual patient depends on the severity of the disease and on the level of untreated intraocular pressure at which the impairment occurred. According to the recommendations of the European Glaucoma Association, the treatment should begin with drugs from groups of medicaments, such as alpha-adrenergic agonists, beta-blockers, prostaglandins and local inhibitors of carbonic anhydrase. If drug therapy is not able to reduce intraocular pressure to the target value, then surgical and laser procedures are used to treat glaucoma.

Multiple sclerosis Multiple sclerosis is an autoimmune disease where the patient’s immune system attacks its own nervous system. More precisely, it attacks myelin, which functions as an isolator and forms a layer around the nerve cells in the brain and the spine. Inflammatory focal points appear in different locations and at different times. These focal points provoke a disturbance in the conduction of nerve signals, and this is why we say that with multiple sclerosis dissemination in time and space occurs. The inflammation leaves scars on the focal points, which gives sclerosis its name. The disease affects in average 30 to 80 people in 100 000 and is most common in northern Europe, northern USA and Canada. Multiple sclerosis mostly affects Caucasians. Women suffer from it more often than men. The frequency of the disease decreases towards the equator mostly due to the differences in climate, sunlight, eating habits, infections and genetic factors.

Your result Decreased risk

Your risk

0,25 %

Population risk

0,50 %

In 30% of all cases the disease occurs in both of identical twins The cause of multiple sclerosis is unknown and is most probably the consequence of a combination of environmental and genetic factors. Even though the disease does not comply with the definition of hereditary diseases it does appear in both of identical twins in 30% of all cases. HLA, the human leukocyte antigen, plays an important role in the development of the disease as well as genes for interleukin, a signal protein which is a part of immune processes, do. The inflammatory process is triggered by activated T lymphocytes which gain access to the brain through damaged blood-brain barriers. These T lymphocytes do not recognize their own myelin and they attack it. The immune process is triggered and it attracts other inflammatory cells and activates additional inflammation mediators like cytokines and metalloproteins. A vicious cycle is formed but the inflammation does subside at times. A phase of regeneration and re-myelisation of the axons occur, however it does not reach the initial state of the brain, as it was before the inflammation. Multiple sclerosis initially occurs only in early attacks (relapses), then subsides (remission), and is called the Relapsing Remitting Multiple Sclerosis (RRMS). The neurological difficulties become later more and more present and this is its insidious progression.

The diagnosis is based on McDonald’s diagnostic criteria which alongside clinical data (the number of flare-ups of neurological attacks) takes into consideration the number of focal points shown on the magnetic resonance image (MRI) of the brain and the spinal cord. Basically it is still an assessment of the course of the disease “in time and space.”

Genes vs Environment

Genes

55%

Environment

45%

Prevention and therapy We donâ&#x20AC;&#x2122;t have yet means of completely preventing or curing multiple sclerosis, but we can affect its progression and ease its symptoms.

Medical advice You have a decreased risk of developing multiple sclerosis. The disease is still incurable, but its development can be impeded with appropriate medications, a healthy diet and an active life style. Multiple sclerosis is a relatively rare disease as on average it affects 3-8 people out of 1000 in Europe. It is most common in people between the ages of 20 and 40, and it is rarer in people of a more advanced age. Even though the disease is still incurable the biological medications therapies are very successful in impeding its development. A healthy diet and an appropriate life style can help enormously. We have determined that you have a decreased risk of developing the disease in comparison to the risk of the average population, which means that your absolute risk is still actually very low.

Patients should avoid excessive physical efforts and should take extra care of their health, mostly by avoiding colds, as infections can trigger the development of the disease. Flu vaccinations are highly recommended as studies show that the vaccination does no harm, i.e. it does not cause the reappearance of the disease. The intake of various foods with lots of vitamins and minerals is highly recommended, as it can improve the disease prognosis. A lot of exercise and maintaining of good physical condition is also useful, as fatigue is an important symptom of the disease. Saunas with a high temperature setting or bathing in hot water can cause the worsening of the symptoms, and this is why staying in extreme heat is to be avoided. Sudden changes to the worse are treated with corticosteroids that help to impede the development of the disease. Biological medications which block and mitigate the immune system have been used in the last couple of years. Among these are primarily interferon beta and glatiramer acetate. Natalizumab, a newer medication, prevents the infected cells from travelling from the blood to the brain, where they cause damage typical for multiple sclerosis. Natalizumab is used in cases of a disease that progresses quickly and when the interferons are not efficient enough. Numerous new medications are already in the last phase of clinical trials.

High blood pressure (Hypertension) The heart and blood vessels have the role of securing the human body with blood and nutrition for all organs. This requires an adequate pressure of the blood to the vascular wall. The blood pressure is carefully regulated, as a blood pressure that is too low affects the transport of matter, whereas if it is too high severe tissue damage can occur. High blood pressure or hypertension is a condition in which the systemic arterial blood pressure measures more than 140 mmHg systolic (top reading) and 90mmHg diastolic (bottom reading). Hypertension is considered to be the world’s leading cause for cardiovascular diseases, which is also the most common cause of death. Hypertension is also called “the silent killer”, as years or, even decades can pass without any symptoms of the disease showing. Unfortunately by the time the symptoms do appear numerous organs are already severely and irreparably damaged.

Your result Average risk

Your risk

39,92 %

Population risk

40,00 %

Hypertension more often affects men

During childhood it is extremely rare. However its frequency grows soon after puberty. Studies show that 40% of adults have a higher blood pressure than normal. Men are affected more often than women mostly because of the higher number of risk factors (smoking, alcoholism) in the male part of the population.

There are two groups

Primary or essential hypertension is most common and it is present in 94% of all cases. We do not know what causes it. Its development is dependent on several factors, for instance age, gender, race and genetic factors. Environmental factors (such as eating habits, particularly salt intake) bear a certain influence as well, as do an individual’s employment situation and their way of life in general. The presence of diabetes is also of a significant importance in the development of this type of hypertension. Cases in which the cause of the disease is known to us belong to the second group, named secondary hypertension. One of the more significant examples is hypertension is caused by kidney diseases and disorders in the function of kidney hormones. The consequences are a disturbance in the regulation of electrolytes, particularly potassium and sodium, and water retention, reflected in the high blood pressure.

Genes vs Environment

The consequences are numerous…

Heart damage is the most serious consequence, as it leads to the weakening of the heart muscle or, most severely, to a heart attack. Damaging of the nervous system is also a possibility manifested as headaches and impaired vision, or a stroke in the worst case. The kidneys are often affected, which leads to an even higher blood pressure. This vicious cycle can lead to complete kidney failure if the condition is inadequately treated or neglected.

Genes

50%

Environment

50%

Prevention and therapy

Medical advice Your genetic makeup determines an average risk for developing hypertension. For this reason we recommend that you closely follow preventive measures. A high blood pressure is no reason to worry, as the treatment of hypertension has a very high success rate. A healthy life style and appropriate eating habits are of the utmost importance for the prevention of hypertension. It is very important to maintain a healthy body weight, to limit your daily intake of salt to less than 2 g, to exercise regularly and, if you are a smoker, to quit smoking. If you do have a high blood pressure and these measures are not enough, then we recommend you to visit your personal doctor, if you haven't done so already. In such a case you should try effective medications for hypertension, which can be taken separately or in combination.

Leading a healthy life is of a crucial significance in prevention of high blood pressure. We ourselves are the only ones who can greatly influence the development of disease: • Maintaining a normal weight is of great importance. • It is recommended to limit salt intake to less than 2 g per day (one teaspoon). • Regular exercise is important as well, for example a 30 min daily walk is highly recommended. • It is important to limit the intake of alcoholic beverages (men 2 dl women 1 dl of wine per day). • Both active and passive smoking should be avoided. • It is advisable to reduce the level of stress. This can be accomplished, for example, by doing various hobbies, or simply walking. • Different chronic conditions such as diabetes, high cholesterol, kidney disease etc. should be appropriately treated. When this type of prevention is insufficient, the doctor can prescribe different types of medication, the choice of which is dependent on the level of blood pressure and the potential presence of other diseases. Diuretics have an impact on the kidneys, allowing the elimination of excess salt and water from the body. The beta blockers reduce the burden on the heart and widen the blood vessels while lowering the heart rate. Angiotensin-converting enzymes (ACE inhibitors) prevent the creation of angiotensin 2, the substance which causes contractions of blood vessels. Inhibitors of the angiotensin receptor 2 are important in the treatment of people with heart or kidney failure. Calcium channel blockers help relax vascular soft muscles. Renin inhibitors block the creation of renin, a substance which produces chain reactions that lead to high blood pressure. In numerous examples the doctor prescribes, besides a specific therapy, a low dose of Aspirin for the prevention of heart complications related to high blood pressure.

Psoriasis Psoriasis is a chronic autoimmune disease that affects the cell cycle of skin cells, making it much faster than in healthy people. In a healthy human body the immune specific T lymphocytes are designed to fight foreign substances such as viruses and bacteria. In the case of psoriasis, T lymphocytes recognize the bodyâ&#x20AC;&#x2122;s own cells as foreign and begin to attack them. Dead skin cells and lymphocytes begin to accumulate, which gives the skin a distinctive look. The skin of people with psoriasis becomes scaly and red. In some cases it appears in the milder form only as a nuisance, while in others it causes a severe systemic disease that may even lead to disability. The diagnosis of the disease is usually sufficiently done thorough medical history and an appropriate medical examination. To confirm the diagnosis, your doctor may withdraw a fraction of the skin, to discover the exact type of the disease and exclude other skin diseases. Skin psoriasis is actually fairly common Research shows that around 3 percent of the general population suffer from psoriasis. It affects people of all ages, but the symptoms of the disease usually appear between the age of 15 and 30. The disease is approximately equal in both sexes and no significant difference has been observed between different races. The exact cause for an immune response against bodyâ&#x20AC;&#x2122;s own cells is not yet known, but there are several factors that increase the chances for disease development. These include infections (angina), skin injuries, such as cuts or severe sunburns, stress, cold weather, smoking, excessive use of alcohol and certain medications. Skin psoriasis is largely a hereditary disease, so essentially the most important risk factor for the disease is its occurrence in the family. Every third patient has a relative who also suffers from the disease. Psoriasis is genetically closely related to the HLA (human leukocyte count antigen) system, which has a role in detecting foreign substances in the body and is located on the sixth chromosome.

Disease appearance Psoriasis may appear cyclically and last for several weeks or months. Remission follows with almost unnoticeable signs and symptoms. The most common feature of the disease is islands of red skin with silvery scales on top of it. In these areas, the skin is dry and chapped. The islands of diseased skin may be small and rare, or they may involve large skin areas. The diseased area may itch, feel warm or be painful. There are also changes in nails, being thickened and raised. Often joints are affected as well (psoriatic arthritis).

Your result Increased risk

Your risk

20,71 %

Population risk

2,50 %

Genes vs Environment

Genes

75%

Environment

25%

Prevention and therapy Regular skin care is essential for patients. We recommend oil baths, special skin creams and ointments.

Medical advice Your risk of developing psoriasis is increased, but your absolute risk is still low as in average population only 2.5 per cent of people are affected with psoriasis. We found that compared to the general population, you have an increased risk of developing psoriasis. It is currently not known how to prevent or cure psoriasis because it is an autoimmune disease with a strong genetic background. If you notice excessive hardened sites on your skin, especially on elbows, knees and scalp, we suggest that you visit a dermatologist. Be careful to notice joint pain and swelling of the small joints, which is also characteristic of psoriasis. For people with psoriasis, it is important to follow general instructions, which can ease the symptoms and reduce the number of occurrences. If necessary, use local and systemic drugs and irradiation.

Patients should live as healthy a lifestyle as possible with as little stress as possible. We do not recommend fat foods, especially consumption of animal fats. Patients should enjoy varied, vitamin-rich foods; eat many fruits and vegetables and unsaturated fats. Enough liquid should be taken in, especially non-carbonated drinks. Taking lecithin and selenium supplements has also favourable impact. We discourage drinking alcoholic beverages and smoking. Moderate natural sunbathing is most beneficial to most patients. Exposure to UV light should be moderate and general preventive measures should be taken. Patients with extensive psoriasis require irradiation of larger skin areas; such treatment is carried out under medical supervision. Staying in some natural spas has a very beneficial effect, characterized by a synergistic effect of many factors such as a friendly climate, relaxation, adequate nutrition, thermal mineral baths (balneotherapy), regular use of remedial and conditioning ointments and also irradiation. Ointments should either contain substances that dissolve scales, are anti-inflammatory or immunosuppressive. In radiation therapy a variety of photo spectra is used. Laser systems that produce high-energy UVB rays of certain wavelength are available. Their great advantage is that they irradiate exclusively the illness. In severe cases, hospitalization is necessary with drugs in the form of pills, injections or infusions. Biological immune-modulatory drugs hold promise to the treatment as well. Recently, a popular alternative therapy has emerged where â&#x20AC;&#x153;kangalâ&#x20AC;? fish eat dead skin, and transfer enzymes to patientsâ&#x20AC;&#x2122; blood, inhibiting the formation of new lesions.

Rheumatoid arthritis Rheumatoid arthritis is a chronic systematic inflammatory disorder which affects mostly small joints of the hands and legs, the wrists and knees. Rheumatoid arthritis develops from an inflammatory reaction and the release of numerous inflammatory mediators. This causes symptoms characteristic of the disease, such as fatigue, the loss of appetite, perspiration, fever, loss of body weight and insomnia. The joint problems occur only later in the disease. Rheumatoid arthritis is spread through the whole world and affects people of all races and ethnic groups, and it affects an approximate 1 percent of all people. It occurs in all stages of life, but mostly between the ages of 30 and 50. Women have a higher risk, as the disease occurs in women three times more often than in men. The differences most likely occur due to the different hormonal influence on the immune system in men and women.

Your result Decreased risk

Your risk

0,41 %

Population risk

1,00 %

The disease has a significant family association The disease is very dependent on the presence of specific HLA antigens. HLA stands for human leukocyte antigen, a protein which is located on the outer cell membrane and is specific for the individual. The immune system uses the HLA antigen for differentiating between foreign and its own cells; however the system malfunctions when autoimmune diseases, such as rheumatoid arthritis, occur. This means that the immune system starts attacking its own organs and tissues. In the case of rheumatoid arthritis the immune system attacks the joint capsule components and causes an inflammatory reaction and the secretion of numerous mediators of inflammation (interleukins, interferon gamma, tumour necrosis factor alpha). The inflammation leads to joint capsule damage which manifests in the symptoms of the disease.

Unspecific disease development The initial symptoms of the disease are very unspecific as they include fatigue, a loss of appetite, perspiration, fever, a loss of body weight and insomnia. The joint pains are not usual in the beginning and manifest only after a certain period of time. Gradually the joints become rigid and they swell. In later stages of the disease malformations occur in the joints of the fingers and wrists, as well as deformations characteristic of the disease.

Clinical examinations and blood analysis are crucial for the discovery of the disease and its diagnosis. The tests performed in the laboratory determine the sedimentation, the C-reactive protein and the presence of some antibodies (rheumatoid factor, anti-dsDNA, anti-cyclic citrullinated peptide antibodies).

Genes vs Environment

Genes

60%

Environment

40%

Prevention and therapy

Medical advice Your genetic analysis has shown that you are carrier of the genetic variants which determine a decreased risk of developing rheumatoid arthritis. Your genetic analysis shows that you have a decreased risk for developing rheumatoid arthritis in comparison to the rest of the human population. Genetic composition greatly influences the disease, but is not the only risk factor. There are other factors which are equally responsible for the development of the disease and remain rather unknown. If the disease occurs in spite of your low risk, it is important to maintain regular physical activity, adjusted in accordance to the disease, as this helps reduce the pain in the joints and improve our general physical fitness. Alongside the antiinflammatory medications, which reduce the symptoms of the disease, biological medications, which greatly influence the diseaseâ&#x20AC;&#x2122;s progression, have become available in recent years.

Rheumatoid arthritis is a chronical disease for which no cure is known. The main cause of the disease in unfortunately unknown as well. One of the possible causes could be infections, as it has been proven that smokers have a higher possibility of developing the disease. Patients can greatly improve their state of health by regular daily physical exercise. Physical exercise improves the flexibility of their joints, their physical fitness and can lessen the pain and swelling. It helps to reduce fatigue, strengthens the muscles and bones and improves the patientsâ&#x20AC;&#x2122; overall well-being. The medications are used to alleviate the inflammatory process in the joints, to lessen the pain, to protect the joint parts and maintain appropriate joint function. Non-steriodal antirheumatic medications help lessen the pain and they are antiinflammatory and antipyretic. Their prolonged use can however have certain unwanted side effects. Glucocorticoids are usually used in combination with other medications and are intended for short term use, as they can cause the decrease of bone density. The therapy withdrawal is a slow process and it must be done under the supervision of a doctor. The so called immunomodulary medications are also available for treatment. The positive effects of these medications are visible several weeks or even months after the patient has started regularly taking them. This is why they are most often combined with the medications described above. In the last couple of years fast-working biological medications have become available; however, due to their high price and unknown side affects is their use restricted to patients who are unresponsive to therapy with immunomodulary medications or who do not tolerate the relatively high dosage necessary for the supervision of inflammation. In case irreparable damage occurs in a joint, surgery becomes an option. The surgery includes the removal of the inflamed inner synovial membrane, a joint replacement, the preleasing of entrapped nerves, etc.

Restless leg syndrome Individuals with restless legs syndrome (RLS) usually describe it as a discomfort in the legs, especially in the calf area, but also in the feet or thighs, leading to the presence of tingling, stinging, tearing, tension, etc. Discomfort initiates when the person wants to rest, especially in the evening in bed, but symptoms may also occur in the car, airplane, theatre; hence wherever inactivity is taking place. In most people with RLS the symptoms worsen especially in the evening when lying down to sleep, and occur often at night and disturb sleep. In Europe, restless legs syndrome affects about 10 percent of people, affecting women twice as often as men. Research shows that lack of iron and dopamine in the brain can be considered responsible, but the underlying cause of the syndrome is still unknown.

Your result Slightly increased risk

Your risk

14,32 %

Population risk

10,00 %

The drawbacks of restless legs syndrome

Unpleasant feelings or the need to move the legs is partially or completely calmed by movement, such as leg stretching or walking. The beneficial effects last at least until the activity continues. Periodical limb contractions during sleep occur in 80 percent of the people with RLS. Insomnia due to the syndrome causes excessive daytime sleepiness and fatigue, which adversely affects the quality of life of affected persons. In the worst cases the symptoms persist during the day. In this case, they cause big problems when travelling, e.g. when sitting for several hours in an airplane or car, or when participating in other social activities such as visiting the theatre or cinema.

The causes of restless leg syndrome

Causes of the disease are mostly unknown. Studies show a correlation between dopaminergic and opioid systems, lack of iron in the brain and rhythms of wakefulness and sleep. In this case we are talking about idiopathic or primary restless legs syndrome.

There are also secondary forms, which are less common. Possible causes for the secondary form can be neurological disease, iron deficiency, diabetes, hypovitaminosis of B vitamins, thyroid dysfunction, rheumatic disease, antidepressants, neuroleptics, and drinking too much coffee and alcohol. Restless legs syndrome is common during pregnancy. It affects 30 percent of pregnant women in the last trimester of pregnancy, after delivery, however, it often disappears.

Genes vs Environment

Genes

55%

Environment

45%

Prevention and therapy

Medical advice Your genes determine a slightly increased genetic risk of developing restless legs syndrome. Simple preventive measures are helpful if this syndrome should actually appear.

Although restless legs syndrome is fairly common, your genetic result still does not mean that you will actually develop the syndrome. In case you begin to see the typical symptoms then the first health measures are rather simple. Avoid stimulants such as coffee and tea, and especially alcohol in the evening. Maintain moderate physical activity and consider going to bed later, when symptoms have largely subsided. When such preventive measures do not help, you should visit your personal doctor, who can suggest a therapy and appropriate medications.

Often even a slight change in living habits might be sufficient to prevent restless leg syndrome. It is recommended to avoid taking stimulants containing caffeine and to consume excessive amounts of alcohol. Moderate physical activity has a beneficial influence, while too much activity can worsen the symptoms. It also helps if you go to sleep later than usual, when the evening symptoms have largely been resolved. When prevention is not enough, it is appropriate to visit your general physician to rule out other possible causes that may worsen or lead to the symptoms of restless legs syndrome. Studies have shown that iron deficiency is associated with increased likelihood of restless legs syndrome. Iron content is determined in the body of the affected individuals by measuring ferritin levels. Ferritin is a protein responsible for iron storage in the body. Taking iron supplements can in this case eliminate restless leg syndrome. Patients with renal failure may also experience the symptoms of restless legs syndrome. As the disorder normally occurs only in the advanced stage of kidney disease, then there is no redundant check of renal function with simple laboratory tests in all patients with restless legs syndrome. About one third of all people with RLS need treatment with medications. Dopamine agonists, that have shown rather effective treatment capacity in practice, are mainly used. Interestingly, one third of pregnant women feel the restlessness in the legs in the last trimester of pregnancy. The cause is not completely understood; the symptoms disappear after childbirth, but can reappear in later life.

Diabetes mellitus type 1 Diabetes mellitus type 1 is also known as juvenile diabetes or insulin dependent diabetes. In this type of diabetes in the pancreas does not produce insulin, a hormone, necessary for the lowering of blood glucose. Diabetes mellitus type 1 characteristically occurs during childhood or puberty and this is why it is also called juvenile diabetes. Both genetic and environmental factors have a great role in the development of diabetes mellitus type 1. These are mostly viral infections which influence the functioning of the immune system. Diabetes mellitus type 1 is an incurable disease which can be successfully managed through an adapted diet and the regular application of insulin. The disease has a good prognosis if it is properly treated and patients suffering from it have a high likelihood of living to an old age.

Your result Decreased risk

Your risk

0,59 %

Population risk

1,50 %

Diabetes mellitus type 1 occurs due to an error in the immune system

The disease, characteristically, is familial type. However it is unknown why the immune system attacks and destroys the pancreatic cells, which regulate the insulin production in the body. The body then develops a lack of insulin and consequently the blood sugar does not arrive in the cells, but accumulates in the blood. Different studies have shown that people with a hereditary predisposition have certain viral infections present, some of which may be the cause of the diseaseâ&#x20AC;&#x2122;s development. The symptoms of diabetes mellitus type 1 are a consequence of heightened blood glucose. The glucose binds water from cells and tissues to itself, and this causes the patients to feel persistent thirst. An increased intake of liquids and frequent urination are both characteristic of the disease. Since there is no insulin in the blood circulation, which would enable the glucose from the food to enter the cells, the patients have an incessant desire for food present even after a large meal. However, they can lose a lot of weight even though their food intake is much higher than normal. Since there is no insulin, the glucose from the food cannot enter the cells. This is why the body starts to use the energy and glucose stored in the liver and the muscles, which is followed by the use of the glucose stored in fat.

Complications 44

An inappropriate regulation of glucose can cause numerous complications. The patients can lose consciousness, they can vomit, have painful stomach cramps, a fever and an acetone breathe. Long-term complications can occur after the disease has been present for several years and numerous organs, such as the blood vessels, heart, kidneys, nerves, and eyes, can be affected.

Genes vs Environment

Genes

80%

Environment

20%

Prevention and therapy

Medical advice We have determined that you have a decreased genetic risk of developing diabetes mellitus type 1. The disease usually appears during childhood or adolescence. Adults have a very low risk of developing diabetes mellitus type 1. Your genetic analysis has shown that you have a decreased genetic risk for developing diabetes mellitus type 1. The disease usually appears during early adolescence and the risk of its development in adults is minimal. Patients suffering from diabetes mellitus type 1 have characteristic symptoms, such as thirst, hunger, a loss of weight and increased urination. The disease is ultimately confirmed with the determination of the glucose concentration in the blood. The development of diabetes mellitus type 1 cannot yet be prevented. The classical treatment with insulin is however highly effective.

There are several studies currently in progress dealing with the potential prevention of diabetes mellitus type 1 in people with a high risk. The studies are targeted towards children with a relative suffering from the disease, as an early detection of the disease is possible with the determination of specific antibodies. It is however still impossible to prevent the appearance of the disease. The blood glucose levels can be stabilized only with a regular insulin use. The amount of the used insulin must be adapted in accordance to the patientâ&#x20AC;&#x2122;s diet and physical activity. The level of glucose in the plasma increases after a meal and more insulin is needed. During a physical activity, the level of blood glucose decreases due to its increased entry into the muscle cells, and the patient needs less insulin. There are several types of insulin and they differentiate according to the duration of their functioning. Those of a short duration are used to balance a high level of glucose after meals, and those of a longer duration are used to ensure a stable concentration of insulin and glucose that could last for 24 hours and to stop the decomposition of fat reserves. The insulin is applied with special pen shaped syringes which allow for a simple dosing of the appropriate quantity of insulin or with the use of insulin pumps, which constantly supply the insulin. Blood glucose measurements are performed multiple times a day and serve as a shortterm inspection of the therapyâ&#x20AC;&#x2122;s success. They are however mostly used before the actual injection, and to determine the appropriate dose of insulin necessary. Appropriate diet is an important part of the therapy as well and is carefully adjusted to the insulin injections. Physical activity lowers the lever of blood glucose and increases the sensitivity of the cells to the insulin. This is why patients are instructed to perform regular aerobic exercise. However, the blood glucose can drop to an unhealthy level during physical activity, so it is important that the exercise plan is carefully designed and that exercises are performed in moderation.

Diabetes mellitus type 2 Diabetes mellitus type 2 is also known as noninsulin-dependent diabetes mellitus. It is a disease characterized by an unsuitable regulation of blood glucose. It differs from diabetes mellitus type 1 insofar that the secretion of insulin in diabetes mellitus type 2 in completely normally regulated, whereas it is the lack of insulin that causes type 1. When ingesting food the level of blood glucose rises and this is why a healthy personâ&#x20AC;&#x2122;s pancreatic cells secrete insulin, which in turn affects the lowering of the levels of blood glucose. With diabetes mellitus type 2 the receptors which recognize insulin are unresponsive to it and the body reacts as if the insulin was never released into the blood stream. Consequently the blood glucose never drops to its initial level. In addition to an unhealthy food intake and an inappropriate way of life, it is your genetic composition which aids this unwanted process.

The cause of diabetes mellitus type 2 is the reduced sensitivity of the cells which recognize insulin Diabetes mellitus type 2 is a worldwide disease which mostly develops after the age of 40. In average it affects every fourth person and its frequency is only rising due to the modern way of life and inappropriate nutrition. Even though the lack of sensitivity of the cells is physiologically unclear, the genetic and environmental factors which prompt the development of the disease are well known. Amongst these are such factors as excessive body weight, inappropriate nutrition, smoking and excessive alcohol intake.

The signs of the disease are seemingly unrecognizable and this is why it can take years to properly diagnose the disease. Some important symptoms of the disease are an increased thirst, frequent urination, a strong sense of hunger, fatigue, impaired sight and lesions that take very long to heal. Diabetes mellitus type 2 is also connected to other medical complications, developed over a longer period of time. Amongst these are such complications as atherosclerotic coronary artery disease, heart attack, heightened blood pressure, nerve damage, kidney damage, damage to the eyes, damage to the feet, osteoporosis and Alzheimerâ&#x20AC;&#x2122;s disease.

Your result Average risk

Your risk

24,49 %

Population risk

25,00 %

Genes vs Environment

Genes

25%

Environment

75%

Prevention and therapy

Medical advice You have an average genetic risk for developing diabetes mellitus type 2. You yourself can do a great deal to prevent its development and mitigate its consequences, and this is why we advise you to take into consideration the preventive measures. Your genetic makeup determines an average risk for developing diabetes mellitus type 2. By adhering to preventive measures you can additionally decrease the possibility of the disease’s development. A healthy life style, an appropriate diet, the maintenance of a healthy body weight, regular physical activity and avoidance of overeating, are crucial for prevention. Any individual can significantly reduce the probability of the disease’s development with these measures. Prevention can also decrease the frequency and seriousness of the complications with people suffering from diabetes mellitus type 2.

Healthy nutrition – your menu should be varied. Eat several small meals instead of a small number of lavish meals. Your food should include a lot of fruits, vegetables and fibre which slows the absorption of carbohydrates. Meals should cover your daily need for energy and no more. You can determine your daily need by multiplying your normal weight (mean should take 100 off from their height in centimetres and women should take off an additional 10%) by 32 (if you do mild physical work), by 40 (if you do moderate physical work) or by 48 (if you do heavy physical work). Avoid alcohol as it is rich in calories, stops the creation of glucose and elevates the danger of excessive lowering of blood glucose and hypoglycaemia. Physical activity – try to exercise regularly. While doing so, favorise aerobic activities such as cycling, fast walking, running, swimming, etc. Maintain a healthy body weight – Your doctor can guide you in finding the perfect diet, exercise routine and body weight maintenance. If you wish he can recommend an appropriate workshop where you will obtain the theoretical knowledge and practical skills regarding a healthy lifestyle. First and foremost, therapy includes the measures mentioned in the preventive section. When this is insufficient, medications are needed. Medications will lower your appetite, slow down the absorption of glucose in the digestive system, inhibit the creation of new glucose in the liver, increase the sensitivity of muscle cells to insulin and accelerate the takeover of glucose into the muscle cells. In later phases of the disease, “exhaustion of beta cells”, as well as the incapability for beta cells to excrete enough insulin, can occur. This is why many patients suffering from diabetes mellitus type 2 need insulin.

Myocardial infarction (Heart attack) A heart attack (also acute coronary syndrome) is a condition in which a sudden obstruction of the coronary artery occurs. The obstruction of the artery causes the blood flow to stop, which can lead to partial or total heart muscle damage. The heart attack is the most common cause of illness and death in both men and women all over the world. Approximately 1.5 million people suffer a heart attack each year, and more than half a million die from it. More than half of the fatal cases happen while the patient is still in the ambulance being driven to a hospital. A heart attack can happen at any time during a personâ&#x20AC;&#x2122;s life. However, the probability does progressively increase as the person ages. On average, every fifth person over the age of fifty suffers a heart attack, as does every second person over the age of eighty. The risk factors for the obstruction are numerous and very complex, the most important being heightened blood fat levels, mostly high LDL cholesterol and a high blood pressure. Other factors include an unhealthy diet, smoking, excessive weight and the presence of diabetes.

If a heart attack is suspected you must immediately call the emergency number (112) The common characteristic of all patients suffering from acute coronary syndrome is chest pain. If a heart attack is suspected you must immediately call the emergency number (112). The patient can take medication which will immediately alleviate the pain: this medication is called nitro-glycerine and it comes in the form of a spray or tablets. If the patient loses consciousness or stops breathing, the resuscitation procedure must be administered immediately. Various manners of treatment are possible after a medical diagnosis. They are classified into surgery procedures and medications.

The disease is recognized according to the patientâ&#x20AC;&#x2122;s anamnesis and the characteristic symptoms of the disease. It is important to recognize the disease quickly as any delay can be fatal. When the patient is in the ambulance or the emergency room of a hospital, the doctor performs an electrocardiography (ECG) which immediately shows the changes on the heart muscle. Alongside the ECG the diagnosis process takes into account the results of blood works which show the presence of certain enzymes in the blood. These enzymes are exclusively characteristic to the heart and show also the amount of damage on the heart.

Your result Slightly increased risk

Your risk

27,93 %

Population risk

25,00 %

Genes vs Environment

Genes

40%

Environment

60%

Prevention and therapy

Medical advice We have determined that you have a slightly increased genetic risk of suffering a heart attack in comparison to the rest of the population. By leading a healthy life you can significantly decrease this risk. We recommend that you scrupulously follow the modern guidelines for a healthy life style. These include quitting the potential smoking habit, avoidance of passive smoking, limiting of alcohol intake, controlling of body weight and cholesterol levels by following a healthy diet, which should include an adequate amount of fruits and vegetables. We recommend that you exercise regularly and manage your daily stress. If you have been prescribed with medication for diabetes, or for lowering blood pressure and cholesterol, then you should take them in accordance to the doctor’s orders. If you have a combinations of risk factors (high blood pressure, high cholesterol levels, excessive weight, diabetes) then you should measure your blood pressure and blood cholesterol levels regularly.

We can significantly decrease the possibility of a heart attack by adhering to preventive measures. A healthy life style is most important, as well as a scrupulous taking of medications, after they have been prescribed by a doctor. A healthy diet – one of the most common reasons for a heart attack is excessive weight and an increased cholesterol level. Food which does not contain animal fat can drastically lower the possibility of a heart attack. Quitting smoking – the risk of suffering a heart attack doubles when you smoke a pack of cigarettes a day. Regular passive smokers (e.g. people whose partner is a smoker) have a 30% higher risk of developing cardiovascular diseases. When a smoker quits smoking the danger of their suffering a heart attack starts to decrease, but it reaches the low risk of a non-smoker only after ten years. Regular blood pressure measurement – it enables an early discovery and treatment of hypertension and lowers the risk of developing cardiovascular diseases. Managing stress – during stress, adrenalin, a stress hormone, is released, and it causes a higher heart rate and contraction of blood vessels, which increases the risk of a heart attack. Moderate alcohol intake – an intake of high quantities of alcohol is connected to a high blood pressure and to an irregular heart rate, both of which are heart attack risk factors. Anti-aggregation medications (Aspirin is the most known) are medications which stop the blood from coagulating and subsequently lessen the possibility of the appearance of blood clots. Beta blockers reduce the heart rate and blood pressure, as well as the need for blood and in this way prevent heart attacks. ACE inhibitors lower the blood pressure and lessen the risk of cardiovascular diseases in patients who had already suffered a heart attack. Statins are medications which reduce the blood cholesterol levels and reduce the risk of cardiovascular disease.

Venous thromboembolism When a blood vessel gets thorn, blood coagulates (makes a clot), which can save a personâ&#x20AC;&#x2122;s life. However, blood clots can form in the circulatory system, interrupting or restricting blood circulation, which can lead to life-threatening situations. The process of blood clump formation is called thrombosis and clotted blood clumps are called thrombi. Thrombus particles can also generate and release embolus (travelling thrombus) that travel in the blood and cause vascular obstructions elsewhere. Thrombosis and embolism are closely related, and that is why the term thromboembolism is often used. Venous thromboembolism includes two related conditions - deep vein thrombosis and pulmonary embolism. Venous thrombosis is a condition where clot or thrombus occurs within the vein, hindering the circulation of blood throughout the circulatory system. Pulmonary embolism is a blockage of the pulmonary artery, which frequently causes clots that travel through the blood and block the crossing of the main pulmonary artery or one of its branches. This causes a variety of pathological changes, which are reflected in the respiratory and circulatory problems.

Your result Slightly increased risk

Your risk

9,22 %

Population risk

8,00 %

A complication with non-specific symptoms and multiple risk factors Venous thromboembolism, in addition to heart attack and stroke, is one of the most common causes of sudden cardiovascular complications. According to some estimates, in U.S. about 300 000 â&#x20AC;&#x201C; 600 000 new cases of venous thromboembolism are discovered annually. Symptoms and signs cannot be distinguished with certainty from other conditions. Main symptoms result from pulmonary embolism. Amongst them are sudden and rapid breathing difficulties, chest pain when inhaling, coughing, and coughing up blood. These signs may also occur with other illnesses, such as pneumonia, acute exacerbation of chronic obstructive pulmonary disease, pneumothorax and some others. 50

There are many risk factors that increase the risk of venous thromboembolism. The most important are blood clotting disorders, prolonged sitting or lying down, immobilization, postoperative state, trauma of pelvis, hip or lower extremities, positive family history and consumption of birth control pills.

Genes vs Environment

Genes

55%

Environment

45%

Prevention and therapy Prevention of the development of venous thromboembolism is associated with preventive measures that reduce the chances of blood clots.

Medical advice The analysis of genes associated with the development of venous thromboembolism, showed that you are a carrier of less favourable gene variants, and thus have a slightly increased risk for venous thromboembolism. Our genetic analysis has shown that compared to the general population you have a slightly increased genetic risk for venous thromboembolism. Measures that reduce the likelihood of blood clots are important in the prevention of venous thromboembolism. You are advised to regularly move between/during prolonged sitting and refrain from wearing tight clothes. When consuming coffee and alcohol, we recommend moderation. If you have associated risk factors, we recommend wearing elastic socks. A major risk factor is obesity, so we recommend regular exercise and a healthy diet with more fruits and vegetables.

After four hours of continuous sitting, the risk of a blood clotting is doubled, so prolonged sitting should be avoided. On longer flights it is recommended to stretch at least once every hour. It is recommended to wear loose-fitting clothes that do not impair blood flow. Drinking coffee and alcoholic beverages, which cause dehydration and lead to more viscous blood, should be avoided. Proper lifestyle that includes regular exercise and a healthy diet, maintaining proper body weight, avoiding smoking and limiting alcohol consumption, has a significant influence on health. In the case of deep venous thrombosis it is recommended to wear special elastic socks. The aim of treating deep vein thrombosis is to prevent further disease progression. Patients are prescribed with drugs called warfarin and low molecular weight heparin, which you inject each day under the skin of the abdomen. After about five days, heparin injections are no longer necessary, warfarin pills though should be taken for several months or years. Pulmonary thromboembolism is treated with thrombolytics, in particular, medicaments meant for dissolving blood clots (streptokinase, tissue plasminogen activator), with anticoagulants, intended for preventing the formation of clots (heparin, coumarin derivatives), and with analgesics and oxygen. Treatment of pulmonary embolism begins immediately after diagnosis. 51

Gallstones Bile or gall is a greenish-yellow fluid secreted by liver cells and it mostly consists of salt, fat and cholesterol. Its main function is the secretion of superfluous substances and the participation the metabolism of fats. One of the problems that can affect the gall bladder is the appearance of gallstones. A gallstone is a crystalline concretion formed within the gall bladder or bile ducts (tube-like structures which carry bile). It usually does not cause any symptoms, but at times can manifest in the form of a sever attack. Gallstones are a serious medical problem in the developed world, as the number of patients constantly increases. The disease occurs most frequently in Western countries, affects any age group and its frequency increases with age. Women are more exposed to the disease than men due to the influence of hormones and pregnancy.

The main cause for the development of gallstones is an imbalance between individual contents in the bile There are two types of gallstones. The most frequent one is the cholesterol type which occurs due to increased undissolved cholesterol in the bile. A mechanism of this sort is most common in people with excessive body weight. The second type of gallstones is a pigment type. The stones are usually characteristically black, mostly because of the excessive percentage of bilirubin in the bile (a special substance formed as an indirect product of protein degradation). The majority of patients suffering from gallstones have chronic problems, but complications and clinical symptoms occur only rarely. The most common symptom of gallstones is a sharp pain in the upper abdomen which can be accompanied by nausea and vomiting. Occasionally, bloating and gasses may appear and in certain cases yellow skin discolouration (jaundice) and vomiting can occur. During the inflammation, fever may be present as well. The other possible complications are the inflammation of the pancreas and an increased predisposition of developing cancer.

Most patients suffering from gallstones usually lack symptoms. This is why a great number of cases are discovered during examinations for other diseases. In order to confirm a diagnosis, a laboratory examination of the blood is necessary (for measurement of a potentially increased number of liver enzymes) and in some cases an ultrasound of the abdomen is used as well.

Your result Slightly decreased risk

Your risk

15,47 %

Population risk

20,00 %

Genes vs Environment

Genes

25%

Environment

75%

Prevention and therapy

Medical advice The analysis of the ABCG8 gene sequence has shown that you have two common copies of the gene present. This genetic makeup is present in 80% of Caucasian people and determines a slightly decreased risk of developing gallstones. Gallstones are usually not dangerous and do not cause severe complications unless they close the bile duct. In the case of bile duct closing, severe symptoms that lead to gallbladder inflammation are developed. Although the development of gallstones cannot be fully prevented, the possibility for their occurrence can be significantly lowered with the maintenance of a normal body weight, the avoidance of fast diets and unhealthy and fat foods and also with regular physical activity. At the moment, the most efficient therapy is still the surgical stone removal of gallstones with a laparoscopic or classic surgery.

Unfortunately, the development of gallstones cannot be fully prevented. Nevertheless, with the help of specific measures, we can easily prevent the degradation and the reappearance of symptoms. The treatment is not necessary for patients who suffer from gallstones and who lack symptoms. It is important to eat low-fat meals and avoid fried and poorly digestible food. If an abdominal attack does appear, it is advisable to follow a low-fat diet. The primary treatment for patients with painful symptoms (painful cramps under the right part of the ribs) is performed with a surgical stone removal with small incisions in the abdomen. This procedure requires short hospitalization and recovery is very fast. The non-surgical procedure of gallstone removal from the bile duct is called endoscopic papillotomy and endoscopic retrograde cholangiopancreatography. The latter is performed with the help of an endscope which is inserted through the mouth and a radiocontrast is injected into the bile duct. This procedure allows the visualization of gallstones in the bile duct and following endoscopic removal. There are other non-surgical treatments with which gallstones can be melted or crushed. In peroral litholysis, acids, such as the ursodeoxycholic acid (Ursosan), are used. The effect of the lysis depends on the size and number of stones. In contact litholysis the methyl tert-butyl ether (MTBE) is applied into the gallbladder through a catheter. The efficiency of this method does not depend on the size and number of stones. The non-surgical treatment method is also lithotripsy where stones are crushed with the use of extracorporeal shock waves.

Genetic risk factors for developing cancer

ancer is one of the leading causes of mortality in developed countries. The majority of cancers can be treated, many also cured, especially if treatment

starts early enough. Cancer development is associated with genetic susceptibility and environmental factors, which means that with an appropriate lifestyle we can also avoid or at least minimize the chances for disease development. Through your Personal genetic analysis you will receive additional information about your genetic susceptibility, which can help in reducing the risk of disease development.

List of analyses

Skin cancer (Basal-cell carcinoma) Lung cancer Colorectal cancer Breast cancer

Skin cancer (Basal-cell carcinoma) Basal-cell carcinoma or basalioma is the most common type of skin cancer and it develops from the basal cells inside the subcutaneous tissue. It is the most commonly diagnosed type of cancer in the world, and it surpasses lung cancer, breast cancer, colorectal cancer and prostate cancer in the number of discovered cases. In Europe there are more than one million new cases of basalioma per year. Obviously the reason for this lies not only in the recognition of the disease, but also in its notation into registries, where the situation is far from optimal. Additionally the occurrence of basalioma in the past 25 years has more than doubled. Approximately two thirds of patients develop basalioma in body parts most exposed to the sun whereas one third develops it in unexposed body parts as a result of genetic predisposition. Basalioma is a slow growing tumour which rarely metastasizes. In most cases it is noninvasive, however approximately half of the patients develop new primary lesions within five years. Most commonly it appears in the upper two thirds of the face â&#x20AC;&#x201C; mostly the nasal area, more rarely on the cheek or forehead.

Dermatologistâ&#x20AC;&#x2122;s caution: there is no such thing as a healthy tan Skin cancer most usually develops in the epidermis, and this is why these tumours are visible to the human eye and easily noticed during self-examination. Clinically it is shown as a shiny, pearly knot, a red eczema or a thickening of the skin. A final diagnosis is based on a biopsy of the cancerous tissue. Each change of the skin which does not heal after an injury, each discoloration of the skin and each change of an existing blemish is cause to alert your personal doctor. Much like with other types of cancer, the early discovery of basalioma infinitely helps the results of the treatment and it makes complete recovery a very real possibility. The most important risk factor for the development of skin cancer is an excessive exposure to the sun and to ultraviolet radiation (UV). It is important to note that the artificial UV radiation in a tanning salon has the same effect as the UV radiation of the sun. Dermatologists caution against exposure to UV rays and warn that there is no such thing as a healthy tan â&#x20AC;&#x201C; every tan is actually burnt, damaged skin. 58

Other risk factors are a light complexion, a positive family medical history, sunburns during childhood, pre-cancerous skin changes and a weakened immune system.

Your result Increased risk

Your risk

40,55 %

Population risk

25,00 %

Genes vs Environment

Genes

20%

Environment

80%

Prevention and therapy

Medical advice In comparison to the entire human population your genetic makeup determines an increased risk for developing basal-cell carcinoma. However, it is important to know that genetic influence is not the only risk factor. Regular and thorough examinations of the skin and mucous membranes are highly recommended, as changes on the skin are visible even before the development of the disease. This enables their timely removal. In the case of an unusual change on your skin such as moles, you should visit your personal doctor. If he notices an unusual formation on your skin, he will recommend that you see a specialist. When you are exposed to the sun, use appropriate clothing and high factor sun blocks. Your exposure to the sunlight should be limited, especially during the summer months, when you should try to avoid direct sunlight between the hours of 11 am and 4 pm. Be extra careful while playing different sports, working in nature, tending to your garden, hiking and skiing.

The most dangerous risk factor, one who plays a very important part in the creation of skin cancer, is excessive exposure to the sun and to UV rays. Individuals with lighter or ginger hair colour are in the highest risk group, along with those who have a tendency to freckles, those with a lighter complexion and those who quickly develop sun burns. Regular self-examination of the skin and mucous membrane is the best preventive measure. If you notice an unusual change in a mole and suspect that it might be cancerous, use the ABCDE rule of pigmentary changes classification. Here A means asymmetry, B means borders, C means colour, D means diameter and E means elevation or the lifting of the mark on the body. Avoidance of artificial UV lights in tanning salons is highly recommended, as well as avoidance of the sun during summer months between 11 am and 4 pm. During walks and exposure to extreme sunlight it is very important to protect yourself with appropriate clothing, headcovering and protective sun glasses. Protect your exposed body parts with protective sunscreens, sun blocks, lotions, milks or sprays. Make sure to apply whichever product you are using in an appropriate quantity and in regular time intervals. When using these products, be careful that you use a high enough protection factor and that they protect you from both UVA (they cause DNA damage) and UVB (they cause sunburn) radiation. Similarly to other types of cancer the risk of fatal forms of skin cancer is reduced by quitting smoking. We highly recommend that you see a doctor if your mole is asymmetrical, if it has uneven borders, uneven coloration, changes or grows rapidly or elevates to the high of the skin.

Lung cancer The onset of lung cancer is influenced by various noxious environmental factors, the most important of which is smoking, as smoking is connected to as many as 90% of all cancer occurrences. In lung cancer, as in all other types of cancerous diseases, the dominant feature is the malignant change in the cells, the building block of all life. The malignant cells multiply uncontrollably, then invade the surrounding tissues, travel into other organs through blood or lymphatic paths, and then settle there and multiply again. Thus the cancerous tissue replaces the normal tissues, causes the blockage of hollow organs, bleeding, and takes nutrition from the whole organism. The cancerous tissue often releases toxic and hormonally active matter, and triggers immune reactions which can have an effect on other organs.

Your result Increased risk

Your risk

17,44 %

Population risk

11,60 %

Lung cancer is the most common cause of death among all cancerous diseases

According to the World Health Organisationâ&#x20AC;&#x2122;s (WHO) estimates, lung cancer is responsible for 5% of all annual deaths, and men are more often affected by it than women. There are numerous risk factors which increase the probability of developing lung cancer, the most important of which is smoking. As much as 90% of all cases of lung cancer are connected to smoking. Experts have proven that the probability of developing lung cancer is 25 times higher than average in people who smoke a pack of cigarettes a day.

The risk has been calculated only for smokers. The general risk of the population of non-smokers is minimal and data shows that it is lower than 0.5%.

A doctorâ&#x20AC;&#x2122;s examination is necessary for the diagnosis of lung cancer

Lung cancer can be manifested with various symptoms and signs. The most common are coughing, difficulties with breathing (dyspnoea) and an inexplicable loss of weight. Only rarely does the patient suffer chest pains, fever, weakness and the presence of blood in sputum. The doctor examines the potential enlargement of lymph nodes in the neck and armpits. An X-ray imaging and a computed tomography of the chest are also performed. Bronchoscopy is however the essential test for the diagnosis, as the doctor uses a special device to examine the airways. The bronchoscope takes a sample of the lung tissue which is later used to determine the type and the stage of malignancy of the lung cancer.

Genes vs Environment

Genes

10%

Environment

90%

Prevention and therapy

Medical advice Your genetic makeup determines that you have an increased risk for developing lung cancer. Since smoking is a major risk factor for developing lung cancer, then due to your genetic makeup we additionally advise you to quit smoking in case you are a smoker. We have determined that you have an increased genetic risk for developing lung cancer in comparison to the rest of the population. The genes are not the only risk factor for lung cancer. Numerous environmental factors have a great influence as well, most of all smoking (both active and passive), several environment pollutants like industrial exhaust, exhaust gases and matters which have been proved carcinogenic (asbestos, arsenic, aromatic hydrocarbons, etc.). The best and obviously easiest prevention is undoubtedly the avoidance of smoking. From the moment we stop smoking the probability for lung cancer decreases. Approximately 15 years need to pass for the risk to drop to the level of non-smoker.

Smoking is the most important risk factor. A smoker’s risk of developing lung cancer increases with an early start of smoking, the duration of the habit and the amount of smoked cigarettes. If you are a smoker then you should consult your doctor about the possible programs like the use of nicotine replacements, such as patches or chewing gum, which can help you quit smoking. Prevention also includes the avoidance of passive smoking, as inhaling of cigarette smoke is almost as harmful as smoking itself. Avoiding carcinogenic substances (asbestos, aromatic hydrocarbons, arsenic, cadmium, and beryllium) and other pollutants from the environment, such as exhaust gases and other industrial waste is also highly recommended. The possible treatments for lung cancer are the following: Surgical treatment – if the cancer is found early enough the cancerous tissue may be removed. Radiotherapy – its purpose is to destroy the mass of cancerous cells with ionizing radiation. The exact location of the tumour is very important as the radiation can damage healthy cells as well. Chemotherapy – has a cytotoxic effect only on the rapid cell division, which is the main characteristic of cancerous cells. Palliative therapy – it is used mainly to try to improve the quality of the patient’s life. Measures are taken to maintain and improve the patient’s lung functioning. These include breathing exercises, learning proper expectoration and breathing techniques. Measures for the maintaining and improving the patient’s nutrition state are also necessary. The patients ingest high protein and high fat foods if they experience weight loss.

Colorectal cancer The large intestine represents the last part of the gastrointestinal tract. It is approximately 1.5 metres long and ends at the rectum. As many other organs or parts of our body, also the large intestine can be affected by cancerous diseases. This type of cancer is called colorectal cancer. It mostly develops with people past the age of 50, while it very rarely affects younger people. In Europe there are almost 38 000 new cases discovered yearly, which means that colorectal cancer is one of the most frequent cancerous diseases. The survival of patients suffering from colorectal cancer improves yearly. This is mostly due to improved operating techniques and the systemic treatment of the disease with medications which are becoming increasingly effective.

Your result Slightly increased risk

Your risk

8,38 %

Population risk

6,00 %

The disease develops as a consequence of genetic and environmental factors The cause for the diseaseâ&#x20AC;&#x2122;s appearance is still unknown. However, it is known that colorectal cancer occurs as a consequence of the combined functions of hereditary and environmental factors. The risk of developing the disease is increased by an unhealthy lifestyle and the ingestion of fat food as well as alcohol, smoking, colorectal polyps and chronic inflammatory diseases. If the disease is present in the family, the risk of developing it is doubled. Colorectal cancer usually develops as a reaction to polyps (an abnormal growth of tissue projecting out of a mucous membrane). Polyps mostly grow on the colon or rectum wall. Smaller polyps do not cause difficulties, while the bigger ones can cause cramps, hard constipation, bleeding, abdominal pain or even a complete intestinal blockage.

Clinical symptoms depend on the size, location and the tumourâ&#x20AC;&#x2122;s expansion. They are frequently followed by abdominal pain, nausea and vomiting, digestive disorders and a feeling of bowels being never emptied, anaemia and the loss of appetite. Numerous patients confuse early symptoms with other digestive disorders. This is why the disease is mostly discovered in its already progressed phase, when the prognosis is poor.

Genes vs Environment

Genes

35%

Environment

65%

Prevention and therapy

Medical advice We have determined that your genetic risk for developing colorectal cancer is slightly increased. Beside your genetic factors, some environmental factors are also important for the diseaseâ&#x20AC;&#x2122;s occurrence. We can use these environmental factors to our advantage and reduce the risk of developing the disease. Both genetic and environmental factors greatly influence the development of the disease. This is why we advise you to eat healthy food rich in fibre, get plenty of exercise, maintain a normal weight, limit the alcohol intake and quit smoking. Early medical examinations are also a part of the preventive measures, as the early detection of colorectal cancer increases the possibility of recovery. This is why it is recommended for people past the age of 50 to see their personal doctor and discuss the possibility of preventive examinations, which enable the early discovery of the disease.

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The main reasons for the development of colorectal cancer in the developed world are the aging of the population, the lack of physical activity and the ingestion of unhealthy foods. It has been proved that regular exercise, maintenance of normal weight, avoidance of excessive alcohol intake and smoking significantly reduce the risk for developing the disease. It is advisable to consume a varied diet with a lot of fruits and vegetables. Food high in fibres increases stool volume and shortens the transit time of digested contents through the intestine. This enables the intestinal mucosa to be in contact with cancerous substances and some bile acids for a shorter period of time. It is recommended to drink alcohol only in moderation (men: 2dcl wine/day, women: 1dcl wine/day) and to avoid active and passive smoking. The main factor for developing colorectal cancer is aging. Before the age of 50 the disease affects only 10% of the population, which means that 90% of patients are between the ages of 50 and 70. The preventive measures are therefore recommended for the entire population. If colorectal cancer is discovered early, there is a great possibility of recovery. This is why more and more countries are introducing national programmes for discovering colorectal cancer. The first phase of the disease treatment consists of a surgical removal procedure of the cancerous tissue. Treatment with radiation, i.e. radiotherapy, is used only before the surgery and for advanced phases when the tumour has already ingrown into the muscle layers and the surrounding brown fat. The systemic treatment of colorectal cancer by using medications (chemotherapy, biological medications) is performed as an additional treatment after the surgery, or when the disease has already spread.

Breast cancer The breast is a special organ, present in mammals, which produces milk, the first and most important nutritional food for a newborn baby. The breast can be affected by numerous diseases which consist of dangerous changes of connective and adipose tissues. Unfortunately, this can lead to a cancerous disease i.e. breast cancer. During the development of this disease the cells, which compose the breast, start to divide uncontrollably. These cells, changed by the cancerous matter, travel to other parts of the body where they settle and continue to grow – they metastasise. Breast cancer is the most frequent disease in women in the developed world as every year it affects 0.1 % of women. The most exposed to it are white women past the age of 35 while in other races the disease is not as frequent. Breast cancer can also affect men; however it is 100 times less common than in women. Risk factors Causes for the development of the disease are not fully known. Nevertheless, there are several factors which contribute to its development, such as: a long period between the beginning of menstruation and menopause, late age at first pregnancy, obesity, a fatty diet, oral contraceptive pills and genetic predisposition. Studies have shown that breast cancer occurs more frequently in close relatives than in random people, connected to changes in the BRCA1 and BRCA2 genes. Recognizable tissue changes are characteristic The most important diagnostic activity is the breast self-examination, which should be regularly performed by every woman. The self-examination is the most efficient way to find potential changes in the breast. In this way breast cancer is discovered in its early phases, when successful treatment is still possible. The vast majority of lumps in the breasts are harmless. However if you do happen to find one it should be examined by a doctor. Other symptoms include a clear or bloody discharge from the nipple, the nipple’s retraction or its stretching in different directions, changes in the size and shape of the breast, flattening of the breast’s skin, and a change in the breast’s skin colour into orange.

Breast cancer can be discovered with additional tests. The best and most frequently used method is mammography or the X-ray imaging of the breast. However mammograms are not completely conclusive. This is why a harmless change can be thought of as cancerous or, even worse, a cancerous formation can be overlooked. Beside mammography an examination with magnetic resonance imaging (MRI) can be performed, as well as a CT and an ultrasound examination of the breast.

Your result Slightly decreased risk

Your risk

10,45 %

Population risk

12,00 %

Genes vs Environment

Genes

35%

Environment

65%

Prevention and therapy When it comes to cancerous diseases it is important to avoid risk factors which can increase the possibility of the cancerous disease’s developing.

Medical advice The analysis has shown that you have a slightly decreased genetic risk of developing breast cancer. In spite of this we recommend regular and detailed self-examinations of the breasts after the age of 20 and immediate reporting of every suspicious change to your doctor. On average every ninth woman develops breast cancer. If breast cancer is discovered early enough then the patient can live an active and healthy life after the finished treatment. This is why regular self-examinations after the age of 20 are incredibly important. The self-examinations should be performed between the 8th and 12th day of the menstrual cycle, when the tissue changes can be easily found by touch. Pay attention to every lump that it lasts longer than a month, as well as to retraction of the nipples or the breast's skin, to potential discharge from the nipples and to every possible change of the breasts' size and shape.

Limit your alcohol intake – there is a connection between alcohol intake and the occurrence of breast cancer, and it is recommended that you drink no more than 1 dcl of wine or 2 dcl of beer a day. Maintaining a healthy body weight – regular physical activity, at least 30 minutes a day, as well as the ingestion of food which is low in saturated fats and high in fibre (fruits, vegetables, and grains) is highly recommended. High levels of the hormone oestrogen are connected to the appearance of breast cancer, and they can form in adipose tissue. Avoid long exposure to hormone therapy during menopause – studies have shown that there is a high risk of developing cancer with the use of a combination of oestrogen and progesterone for a period of time longer than 15 years. The same is true for hormone therapy after the age of 60. Avoid pesticides – organochlorides, a group of pesticides which includes a prohibited pesticide called DDT, can bind themselves onto the same receptors as oestrogen. Women who have a higher risk of developing breast cancer (due to the presence of the disease in the family) must also take into account the following: Chemoprevention – Tamoxifen is used with women over the age of 35. It manages to lower the risk of the development of non-invasive breast cancer by a third and the development of invasive breast cancer by half. Raloxifene is used with women who have a higher risk during menopause. Radical surgery – the removal of one or both breasts. This type of procedure is used with women who have already suffered from breast cancer on one breast, who have a positive family anamnesis, a positive genetic test, or have had the early form of breast cancer discovered by a doctor.

Medicament response

ellular proteins are a frequent target of medications. This means that a specific medication must successfully bind with the targeted protein in order

to achieve a positive effect. Differences in the genetic code can cause this protein to differ in different people. This is strongly influences the efficacy of the treatment. Numerous studies have shown that, beside clinical factors such as the age, gender, body weight, current health and liver function, the genetic factor is by far the most important one when it comes to the response to medications. Every other person in the population carries certain genetic variations which can alter the effects of medications.

List of analyses

Clopidogrel - prevention of blood clotting Metformin - regulation of blood sugar Omeprazole - inhibition of gastric acid secretion Perindopril - treatment of stable coronary artery disease Statins - lowering blood cholesterol Warfarin - prevention of blood clotting

Clopidogrel - prevention of blood clotting When we cut ourselves, the body responds with a complex physiological process that leads to blood clotting. The mechanisms present in the case of cuts or other injuries are meant to prevent blood loss, while blood clotting within intact vessels can lead to clogged arteries and heart or brain attacks. People who are subjected to unwanted blood clotting in the blood vessels take clopidogrel, a drug belonging to the thienopyridine class usually prescribed in combination with aspirin. Regular administration of clopidogrel prevents potential blood clotting, which could clog arteries and provoke a heart attack or a stroke. Clopidogrel is an antiplatelet drug because it works on platelets and prevents their aggregation. It is also used with people suffering from peripheral arterial disease, with those who have unstable angina as well as with those who have intracoronary stent.

The mechanism of clopidogrel activity

Clopidogrel is a therapeutic substance in the form of a pro-drug. This means that this substance needs the help of specific enzymes in the body to convert it to the active form otherwise the administration of clopidogrel has no effect. The aforementioned activation is primarily mediated through an enzyme called CYP2C19, which is found to be defective in more than a third of all Caucasians. The effect of clopidogrel is insufficient or it has no effect on people who are carriers of a gene variant known as CYP2C19*2. These individuals have lower circulating concentrations of the active substance or don’t have it at all. Therefore, the risk of cardiovascular complications will not be reduced to the desired level after administrating the drug. FDA (US Food and Drug Administration) ordered the manufacturers of Plavix (with active ingredient of clopidogrel) to add a special warning on the medications, stating that the efficacy depends on the individual’s genotype and that for a certain group of people there will be no favourable therapeutic response to the treatment. Therefore various alternatives, such as aspirin monotherapy or adjunct use of other antithrombotic drugs (prasugrel, ticlopidine), are recommended for people with impaired CYP2C19. On the other hand, people with the gene variant known as CYP2C19*17 have an increased risk of bleeding upon clopidogrel administration. However, for the CYP2C19*17 genotype, there are no recommendations or guidelines for dosage modification nor have any alternative medications been suggested.

Your result Less efficient metabolism of clopidogrel One of the two copies of your CYP2C19 gene encodes an inactive enzyme. This is why you are likely to need a replacement of clopidogrel therapy with alternative treatments. We have examined two sites within the CYP2C19 gene that influence the activity of the enzyme. No changes occurred on the site that affects the lower enzyme CYP2C19 activity. While on the other site, which results in a decreased activity, one of the two copies has been mutated. The conversion of clopidogrel from the inactive form to the active form is slower in you due to a partially defective enzyme, so the clopidogrel is less effective for preventing the formation of blood clots. In case you would ever need therapy with clopidogrel, the doctor should be informed that you belong to the group of intermediate metabolizers, meaning that the drug is not as effective on you as on subjects with non-defective CYP2C19. A number of studies suggest that prasugrel is a more appropriate drug in this case.

Tradenames of drugs Clopidogrel: • • • • • • • •

AGRELEX CLOPIGAMMA DUOPLAVIN KLOPIDOGREL PICTURLOP PLAVIX PONTIUS ZYLT

Metformin - regulation of blood sugar Your result Average likelihood of metformin effectiveness According to the result of your genetic analysis, you belong to a group of people for whom the therapy with metformin shows an average effectiveness.

You are a carrier of such an allelic combination of the SLC22A1 and C11ORF65 genes that determines an average functioning of metformin for the treatment of diabetes type 2. Research has found that for subjects with your genotype, the therapy with metformin is more successful than for those with an unfavourable combination of alleles. In your case a slightly greater reduction of glycated haemoglobins is observed, which is the sign of a successful therapy. However, the function and effectiveness of metformin is also influenced by other, non-genetic, factors. In the case of diabetes type 2, the doctors take into account the results of blood tests (blood glucose and HbA1c levels) before prescribing the appropriate medication.

Tradenames of drugs Metformin: • • • • • • • •

AGLURAB AVANDAMET EUCREAS GLUCOPHAGE GLUCOVANCE METFOGAMMA METFORMIN AUROBINDO SIOFOR

Omeprazole - inhibition of gastric acid secretion Stomach problems are often manifested as upper abdominal pain, bloating, tickling cough, belching and heartburn. Most of this happens due to the imbalance between the protective layer of the stomach lining and stomach acids, a result of various factors, such as smoking, a poor diet, stress and drinking too much coffee. However, a balance should be restored. This can be achieved with drugs that either reduce gastric acid secretion or enhance the protective layer of the mucous membrane, which is directly connected to the acid in the stomach. The common choice is omeprazole, a drug belonging to a group of proton pump inhibitors that inhibit gastric acid secretion. It is mainly used to prevent ulcers in the stomach and duodenum associated with the use of NSAIDs (non-steroidal anti-inflammatory drugs), and in combination with appropriate antibiotics to treat ulcers of the stomach and duodenum caused by the bacteria H. pylori.

The mechanism of omeprazole activity

Omeprazole is a therapeutic substance of a weak base and it performs as a pro-drug. The drug concentrates within the parietal cells in the highly acidic environment of the intracellular channels where it is being converted to the active form, which affects the final stage of gastric acid formation. More specifically, it irreversibly impairs the functioning of the ATPase acid pump, inhibiting their secretion in the stomach lumen. However, omeprazole is not an effective medication for all people. In some people the CYP2C19 enzyme is highly active, leading to a premature inactivation of omeprazole, which in result does not fulfil its duties. The final omeprazole inactivation is done in the liver via the CYP2C19 enzyme and it depends on the possible presence of mutations in the CYP2C19 gene. Various studies have shown that almost two-thirds of the Caucasian population has an increased activity of the CYP2C19 enzyme, which is responsible for the fast inactivation of omeprazole. This is then reflected in the reduced effect of the drug and in insufficient inhibition of gastric acid secretion. While taking omeprazole, attention must be paid to its possible combined use with clopidogrel. Omeprazole “occupies” the CYP2C19 enzyme, which makes it unavailable to convert clopidogrel into an active form. In this case, clopidogrel can be expected to be less effective in preventing blood clotting.

Your result Effective function of omeprazole You are the carrier of one normal and one rare copy of the CYP2C19 gene that encodes a less active enzyme. However, this has no effect on the metabolism of omeprazole, so therapy is recommended at a normal dosage. We have examined two sites on the CYP2C19 gene. No changes occurred on the site that affects the higher activity of the CYP2C19 enzyme. While on the site, which results in a decreased activity, one of the gene copies has been mutated. However, for the therapy with omeprazole the ordinary dosage is recommended. For the efficacy of omeprazole it is not particularly important that the CYP2C19 enzyme should rapidly inactivate the drug, as people with a less active enzyme are in no danger in any way. It has been proven that 92% of people with your genotype are successfully treated with the standard omeprazole-based antibiotics therapy for duodenal ulcers caused by the bacteria H. pylori.

Tradenames of drugs Omeprazole: • • • • •

GASEC OMOLIN ORTANOL ULTOP ULZOL

Perindopril - treatment of stable coronary artery disease Your result Perindopril is an effective treatment You are a carrier of the AT1 and BK1 gene combination, which determines that the therapy with perindopril will be successful.

Studies have shown that the risk of having a heart attack from coronary artery disease is reduced in people with your genetic makeup when treated with perindopril. You are advised to forward this information to your personal physician in case of stable coronary artery disease. If you have been prescribed perindopril, we strongly recommend using the product regularly and consistently in accordance with the instructions of the doctor. In addition, a healthy lifestyle, plenty of exercise, stress management, smoking cessation, moderate alcohol consumption and a healthy diet will further reduce the risk of complications in stable coronary arterial disease.

Tradenames of drugs Perindopril: • • • • • • • • • •

BIONOLIPREL BIOPREXANIL BIPREXANIL COVEREX PERCARNIL PERINDOPRIL PERINEVA PRENEWEL PRESTANCE TERAXANS

The heart is a tireless pump that supplies all tissues and organs with oxygen and blood through the vascular system. For it to work smoothly the heart must be put first in line for proper nutrient and oxygen supply. As a result, every illness of the heart or coronary arteries that feed the heart, will lead to serious health consequences. Because of this, many medications are used for the treatment and prevention of further cardiovascular complications. One of them is a drug called perindopril, which belongs to the group of ACE inhibitors. It is one of the most commonly prescribed drugs. It is mainly used to treat high blood pressure, symptomatic heart failure and to reduce the risk of cardiovascular events in stable coronary artery diseases.

The mechanism of perindopril activity The hormone renin-angiotensin-aldosterone system (RAAS) regulates blood pressure and electrolyte balance in our body. Renin breaks angiotensin down into angiotensin I, which is then converted to angiotensin II through the angiotensin converting enzyme (ACE). The latter stimulates the secretion of the hormone aldosterone, which causes sodium reabsorption in the kidneys, thereby increasing the volume of fluid in the body and consequently increasing blood pressure. Several medications in the RAAS system are used for lowering blood pressure. One of these, perindopril, inhibits the ACE enzyme activity. Perindopril helps lower the level of angiotensin II in plasma, leading to an increased plasma renin activity (by blocking the negative feedback of renin release) and reduced secretion of aldosterone. Perindopril can lower the blood pressure directly or with the help of some other mechanisms and it can prevent worsening of coronary heart disease and other vascular events. Studies have shown that there is a colleration between the AT1 (the gene for the angiotensin II receptor, subtype 1) and BK1 (bradykinin receptor gene, subtype 1) genes and the effectiveness of perindopril in stable coronary artery disease.

Statins - lowering blood cholesterol Statins are medications that effectively reduce blood cholesterol (inhibit cholesterol production in the liver) and thus prevent the occurrence of strokes and heart attacks. They are one of the most commonly prescribed drugs that are regularly taken by over 32 million Americans. A lot of people today have high cholesterol levels due to the modern style of life that consists of a lot of stress, constant rushing and eating unhealthy foods. This is an important risk factor for cardiovascular diseases and stroke as cholesterol accumulates in the vascular walls, narrowing them, which leads to a disturbed blood flow and damage to the brain or the heart. The level of cholesterol can be largely influenced by a proper diet and regular exercise. These precautions, however, are not enough in the case of an inadequate regulation of the formation of cholesterol in the liver cells. If this happens it is necessary to take appropriate medication according to the doctors’ instructions.

The mechanism of statins activity

Statins are medications that inhibit the activity of the liver enzyme HMG-CoA (3-hydroxy-3methylglutaryl-coenzyme A) reductase, an enzyme which regulates the rate of cholesterol synthesis in the liver cells. After oral ingestion, the liver cells will come to “lack” cholesterol, a necessary component for the formation of bile acids, and will increase the number of cell surface LDL (low-density lipoprotein) receptors. These receptors draw cholesterol from the blood into the liver cells. This is an important factor for atherosclerotic vessels as it diminishes the concentration of cholesterol in the blood. Statins also reduce the production of VLDL (very lowdensity lipoprotein) lipoproteins, which are the main carriers of triglycerides in the blood. They also have protective properties on the walls of blood vessels not directly related to controlling the level of blood fats. The actual effectiveness of statins depends largely on the SLCO1B1 gene. The SLCO1B1 product is a trans-membrane protein that regulates the removal of statins from the blood and their uptake in the liver cells. It has been shown that carriers of certain variants of this gene have four times the risk for myopathy (muscle disease), one of the most frequent side effects of taking statins. Symptoms of muscle myopathy usually develop four weeks after the initiation of therapy with statins and manifest in the form of exhaustion, fatigue and muscle aches of limbs. Carriers of the unfavourable forms of the gene should refrain from taking certain drugs from the statin group containing the active ingredients such as simvastatin, pravastatin or atorvastatin and replace them with fluvastatin, which is a safer alternative.

Your result Normal likelihood for developing myopathy You are the carrier of two normal copies of the SLCO1B1 gene, so for you it is completely safe to take medications from the statin group that contain active ingredients pravastatin, simvastatin or atorvastatin.

Statins are drugs that people with high cholesterol levels usually take all their life. Their regular intake reduces blood cholesterol levels and prevents the development or worsening of coronary heart disease and heart attacks. Most commonly prescribed drugs in the statin group are pravastatin, simvastatin and rosuvastatin. A certain group of people may develop myopathy while taking these medications. This is why it is advisable for them to take the alternative substance fluvastatin instead. However, you belong to a group of people for whom the substitution with alternative medications is not necessary. If your doctor prescribes you statins, take them regularly and consistently in accordance with the instructions of the doctor.

Tradenames of drugs Atorvastatin: • ATILEN • ATORIS • CADUET • SORTIS • TORVALIPIN • TULIP Fluvastatin: • FLUVASTATIN • GALISTAT • LESCOL • VUYATOR

Pravastatin: • PRALIP • PRAVASTATIN Rosuvastatin: • COUPET • CRESTOR Simvastatin: • ACTALIPID • INEGY • SIMVASTATIN • SINVACOR • VABADIN

Warfarin - prevention of blood clotting Your result Lower starting dosage of warfarin Due to the combination of your genes, you will need a lower starting dosage of warfarin.

If you ever need treatment with warfarin, the following information will be useful to the doctor who will prescribe the initial dosage. Because of your VKORC1-1639/3673 AA, CYP2C9*1/*1 genotype, you will most likely need a lower starting dosage than average. If you start therapy with a conventional warfarin dosage, you are likely to experience unwanted bleeding. However, the doctor must not forget that in addition to genetic factors, also other factors (such as age, weight, diet, other medications) influence the dosage.

Tradenames of drugs Warfarin: • • • • • •

MAREVAN COUMADIN JANTOVEN LEWARIN WARAN WARFAN

Warfarin belongs to a group of medications used to prevent blood clotting (these medications are called anticoagulants). Warfarin is used to prevent blood vessels from becoming blocked with blood clots, an event that can result in the obstruction of veins or in a heart attack. It is also used for the prevention and treatment of deep vein thrombosis. Setting the appropriate initial dosage is the major problem with warfarin prescription, as the right amount can greatly vary between individuals. Internal bleeding can occur in the case of the starting dosage being too high, and the initial dosage being too low, there is an increased risk of blood clotting. Generally, the appropriate initial dosage for each individual depends on their gender, age, body weight, and especially on the genetic code of the genes VKORC1 and CYP2C9, which determine the effectiveness of warfarin metabolism.

The mechanism of warfarin activity Warfarin is a medication that inhibits the formation of the blood factors necessary for blood clotting, leading to a prolonged clotting time. The full effect of warfarin is monitored by measurements, which show the speed of blood clotting in the INR (international normalized ratio) units. The results of these measurements are apparent only after a few days of drug administration. Only then can your doctor adjust the warfarin dosage according to the results of the measurements. The effect of warfarin depends on the age, weight, diet, effect of other drugs and on the genetic makeup, where the genes VKORC1 and CYP2C9 play an important role. VKORC1 encodes an enzyme which is normally suppressed by warfarin, and CYP2C9 encodes an enzyme which is responsible for warfarin metabolism. Research has shown that it might be necessary to raise or lower the initial dosage of warfarin as much as 40 per cent depending on individual genetic makeup. A mutation in the VKORC1 gene causes the production of a less active enzyme. For people with this genetic makeup a lower starting dosage of warfarin is needed. The gene variants of CYP2C9*2 and CYP2C9*3 significantly reduce the rate of warfarin metabolism, resulting in higher concentrations of the drug in the blood, and consequently also a lower dosage of warfarin necessary in the beginning of treatment.

Genetically determined physical features and traits

ou are already familiar with most of your talents and abilities but with a genetic analysis, you may discover some new and hidden talents or features

encoded in your genes. For example: you may learn whether your muscular structure predispositions are more similar to sprinters or rather to long distance runners, are you prone to nicotine dependence, or are you very sensitive to pain etc. You can further promote and properly develop your abilities by learning about these features.

List of analyses Eye colour Sensitivity to pain Muscle structure Nicotine addiction Resistance to infection with noroviruses Resistance to malaria (type Duffy) Perception of bitter taste Alcohol metabolism Caffeine metabolism Lactose metabolism Episodic memory Type of earwax Learning from mistakes

Eye colour Eyes differ in the colour of the iris, which may appear brown, green, blue or a completely different colour, such as red. Unlike other analyses, where the potential to develop a disease or trait, in addition to genes, is greatly influenced by our way of life, eye colour cannot be affected because it is a property solely defined by our genes. The main gene that determines the colour of eyes is HERC2. Scientists believe that this gene affects the activity of a nearby gene OCA2 (oculocutaneous albinism II). The product of the OCA2 gene is a trans-membrane protein that regulates the transport of tyrosine â&#x20AC;&#x201C; an amino acid that is a precursor for melanin. The HERC2 gene function regulates the production of melanin through tyrosine transport and this is reflected in different shades of eyes. The more melanin there is in the iris of the eye, the darker the eyes look.

The iris has the same importance for the eye as the lens for the camera

In the iris we distinguish the front and rear epithelial layer. Melanin pigment is located in both layers and its amount varies notably in the front epithelial layers. There is a lot of melanin in brown eyes, less in green eyes and the amount is even smaller in blue. An interesting example is red eyes. The amount of melanin is negligible in the case of red eyes. As a result, light reflects from the capillaries, which are located inside the eyes, giving red colouring to the eyes.

Researchers have shown that many genes affect the colour of your eyes. More recent studies established a link between iris colour and the HERC2 gene. This gene is important because of its effect on the OCA2 gene, which encodes for the protein P. It is a trans-membrane protein that determines the transport of tyrosine, the amino acid precursor of melanin and thus determines its quantity. In addition to the HERC2 gene, some other genes are known to affect the colour of our eyes, but the HERC2 gene has the strongest impact. If you have brown eyes because of a particular form of the gene HERC2, the influence of other genes is miniscule, because they largely determine the brighter shades of eyes.

Your result 72% chance of blue eyes, 27% chance of green eyes, 1% chance of brown eyes Genetic analysis has shown that you are a carrier of two common copies of the gene HERC2. Most people of Caucasian origin have such genetic makeup, while it's actually completely absent in Asian and African populations. Your genetic makeup determines a 72 percent chance that you have blue eyes. Despite the high probability of blue eyes, there is still a 27 percent probability of green eyes and the likelihood of brown eyes is only one percent. This means that out of 100 people with your genotype on average 72 people are born with blue eyes, 27 people with green eyes and one person with brown eyes. Eyes of new-borns are usually blue, regardless of the genetic makeup. Sun exposure induces the production of melanin in the iris, so the actual eye colour of children is finalized at six months of age.

Sensitivity to pain Your result Average sensitivity to pain The SCN9A gene is associated with controlling the level of pain that an individual detects. Your analysis has shown that you are a carrier of two common copies of the SCN9A gene, which determines that your perception of pain is normal. Perception of pain was probably developed during evolution as a security mechanism to detect danger. The extent to which the human perception mechanism for pain is perfected can well be seen when we burn ourselves. We actually withdraw the hand before the information travels to the brain, meaning that we withdraw the hand before we could get burnt. This is due to a specific defence mechanism called reflex with which we protect ourselves from danger before we realize it. Your genetic makeup determines an average pain perception, which means that compared to other people, whose perception of pain is more intense, you tolerate some more pain.

The International Association for Pain Studies has defined pain as an unpleasant sensory and emotional perception associated with actual or potential tissue damage. However, the cause of pain is not always tissue damage nor is tissue damage necessarily accompanied by pain. Pain perception happens through excitation of specific pain receptors. These receptors are the final parts of the pain nerves in which a sufficiently strong mechanical, chemical or thermal stimulus triggers electrochemical potential, which is transferred further via nerves to the central nerve system. Pain can be perceived as dull or sharp, depending on the thickness of the nerve fibres, which were stimulated in this way. Sharp pain differs from dull pain in a way that the individual can tell exactly where it hurts, while with dull pain it is difficult to identify the exact site of pain.

Genetic background and physiology

Although the precise mechanisms of pain perception are still not fully clear, there is evidence that some gene variants affect the perception of pain intensity. Scientists revealed that the sensitivity to pain varies greatly among some individuals. They found that in some people there is a mutation in the sequence of the gene SCN9A, which is reflected in the varying perception of pain. The SCN9A gene is important for the formation of sodium channels, which are important factors for nociception (nerve signalling, in response to a number of potentially harmful environmental factors). Thus, the gene SCN9A regulates the strength of pain through sodium transport. It is a well-known fact that women are more sensitive to pain than men, as shown by special brain imaging. Research shows that the difference occurs mainly due to sex hormones, as for example in women the threshold of pain varies with the phases of the menstrual cycle. 81

Muscle structure There are two different types of muscles, called type I and type II. Sprinters have more type II muscle in their body â&#x20AC;&#x201C; these are fast muscle fibres, intended to be more active. Longdistance runners are expected to have more Type I muscles - slow muscle fibres. Slow muscle fibres produce energy primarily by cellular respiration and their main source of energy is fats. These muscles tire slowly and have red colouring due to a substance called myoglobin. Fast muscle fibres on the other hand, are rich in glycogen and their main source of energy is not fat, but the basic building blocks of glucose and creatine phosphate. Due to a lack of oxygen in fast muscles, lactic acid accumulation occurs, which leads to muscle tiredness.

Genetic background of muscle structure

Scientists researching neuromuscular diseases discovered the gene alpha-aktinin-3 (ACTN3), whose product is important for the contraction of muscle cells. They revealed that the ACTN3 gene product is present only in fast muscle fibres. They identified mutations that cause the gene product to deactivate, resulting in the absence of ACTN3 in these people. They discovered that sprinters have mostly two functioning copies of the gene ACTN3, while long distance runners have two inactive copies of this gene. Other studies have shown that fast contracting muscle fibres, in which the gene ACTN3 is not functioning, consume more oxygen, which slows down muscles. Such fibres would be weaker and smaller but would also tire later.

Another gene, called PPAR is also known to influence the structure of muscles. In slow muscle fibres it regulates the activity of genes that are responsible for fat oxidation. Endurance training increases the burning of fat and gene PPAR alpha increases the oxidative capacity of muscles. Mutations, which affect the activity of the gene and also the relationship between fast and slow contracting muscle fibres in your body, are known in this gene. An altered gene sequence has a negative effect on PPAR alpha activity in slow contracting muscle fibres, and it determines a reduced percentage of slow muscle fibres and increased percentage of fast muscle fibres in our body.

Your result Increased muscle endurance Your genetic analysis has shown that you are a carrier of such ACTN3 and PPAR alpha gene sequences, which give you a predisposition to be more successful in sports where endurance is required, similar to long distance runners. Your genotype determines that you are more successful in activities which require endurance and less in activities where it is necessary to show power and explosiveness. This means that you have durable, slow contracting muscle fibres. Your genetic makeup does not limit you to any form of sport, so you should choose the activity that you like the most. However, you are likely to do better in activities such as long distance running, cross country skiing, aerobics, biking, rollerblading, swimming, climbing or hiking.

Nicotine addiction Your result Increased risk for addiction Your risk for nicotine addiction is increased because you have two unfavourable copies of the CHRNA3 gene. About 15 percent of the population has such a genetic makeup. If you are a smoker, then you are more likely to become dependent on nicotine and experience more difficulties when trying to quit smoking. In case you are not a smoker, we advise you not to experiment with smoking, as people with your genotype are more susceptible to nicotine addiction and quickly become accustomed to cigarettes. If you already have an addiction, then try to replace your favourite brand of cigarettes with the brand that you like the least. Do not buy cigarettes to keep on stock. Before lighting a cigarette, drink a glass of milk, as milk in the stomach will reduce the urge to smoke. We recommend that you consult with your personal physician, who will further advise you on how to quit smoking.

Smoking is one of the most common harmful habits, as there are about 1.1 billion regular smokers in the world. Smoking is proven to cause many serious diseases and is thus also associated with premature death. Statistics show that every tenth man or half of regular smokers in the world die from diseases resulting from tobacco use. The reasons to start smoking are often quite simple, but as dependence is developed quickly, harmful effects can develop quickly. The substance called nicotine is the main reason for such a fast development of addiction. Nicotine makes smoking pleasurable and that is the reason why 50 percent of the people who start smoking during adolescence become regular smokers. Nicotine is the compound responsible for addiction at the molecular level. It binds to specific receptors in the brain and causes a feeling of comfort and pleasure. These receptors differ between people, providing a different risk for addiction.

Genetic background and physiology

Nicotine addiction is a complex phenomenon, which depends mainly on the absorption and metabolism of nicotine. Our genetic makeup, in addition to sociological factors, has a particularly important impact as it can explain more than 50% of the total risk for nicotine addiction. In addition to already known genes with great effect, such as CHRNA3, scientists are trying to discover new genes with smaller effects, so that they could even better understand the biological mechanisms of addiction. Nicotine acts on the acetylcholine receptor family in the brain because it is structurally similar to the brainâ&#x20AC;&#x2122;s chemical transmitter acetylcholine. Binding nicotine on such receptors triggers an opening of ion channels in the cell membrane and the release of new neurotransmitters in the brain, causing a feeling of comfort. Chronic exposure to nicotine causes changes in the receptors, making them less sensitive or even inactive. Eventually changes are made in the metabolism of the nerve cells. All these changes can cause the smoker to fall into abstinence crisis, when quitting smoking.

Resistance to infection with noroviruses Noroviruses, also known as Norowalk-like viruses, are one of the main reasons for nonbacterial epidemic inflammation of the stomach and small intestine. This condition is also known as stomach flu, or gastroenteritis. These viruses cause outbreaks in closed communities, such as families, schools, military and elsewhere, where there is a large concentration of people. Noroviruses are a major cause of inflammation of the lining of the stomach and intestines. They are transmitted by water and food, contaminated with human or animal faeces, through contact with infected surfaces and through direct contact with an infected person. The virus spreads rapidly from person to person due to the simple ways of spreading and infects large numbers of people. However, despite this rapid mode of spreading and infection, a percentage of people does not get infected or develop typical symptoms of infection in spite of the exposure.

In the United States, Noroviruses cause 23 million infections, 50 000 cases of hospitalizations and 300 deaths

Symptoms of gastroenteritis include nausea, vomiting, diarrhoea, cramping abdominal pain, fever and weakness. These symptoms are usually shortlived and resolve within 48 hours. Most patients do not require professional help. Exceptions are children, who are more sensitive to diseases, and elderly patients with chronic conditions, which require control. A norovirus is highly infective, but some people donâ&#x20AC;&#x2122;t get infected even when exposed to it. The FUT2 gene is responsible for this resistance. This gene encodes for proteins called carbohydrates H type 1, which can be found in the mucosa of the gastrointestinal tract and are excreted in the mucilaginous glands. In 20 percent of Europeans these proteins cannot be found due to mutations in both copies of the FUT2 gene, so an entry of the virus into the body is not possible and consequently infection wonâ&#x20AC;&#x2122;t occur. Resistance to an infection with noroviruses has certain advantages as well as disadvantages. Resistant people have a smaller chance of being infected with HIV, while they are more exposed to infection with bacteria, such as E. coli. Problems can also occur with breastfeeding mothers who are resistant to virus infection. If the child does not have the same genetic resistance, as the mother, then protection against infection requires antibodies. Since the mother does not produce antibodies the child is more susceptible to infection.

Your result You are not resistant to the infection Your genetic analysis has shown that you are a carrier of one rare and one common copy of the FUT2 gene, which determines that you are not resistant to infection with noroviruses. About 50 percent of people in the Caucasian population have such The FUT2 gene is important for genetic resistance to infection with noroviruses. It encodes for a specific protein, which is located on the mucous membranes in the digestive tract and through which the Norovirus enters our cells. You are the carrier of one rarer copy of the gene which determines a low level of protein that nevertheless allows noroviruses to enter your cells. Consequently, you are not resistant to infection with the most common noroviruses and are likely to develop symptoms of infection at first contact with the virus. Resistant people have a slightly lower risk for HIV infection, while they are more exposed to infection with bacteria, such as E. coli.

Resistance to malaria (type Duffy) Your result You are not resistant to infection The analysis of the DARC gene, which encodes for the Duffy antigen, reveals that you are the carrier of two common copies of the gene. This genetic makeup is associated with susceptibility to Plasmodium vivax and knowlesi infection, which would cause malaria. Your genetic makeup determines the formation of Duffy antigens that are expressed on the surface of red blood cells, making you non-resistant to malaria. The risk of infection with malaria may be reduced with insect repellents, with the use of insecticidal sprays on the premises or with mosquito nets, which have additional mosquito spray coating. There are also anti-malarial tablets, which require a specific dosing regimen. It is essential to consult your doctor or pharmacist before the use of those tablets, as they can have many side effects. It is also advisable to drain standing water, because this is a frequent place for mosquitoes to deposit their eggs.

Malaria is one of the most common infectious diseases, infecting about 200 million people annually. It is widespread in tropical and subtropical regions, including parts of the Americas, Asia and Africa. It is an enormous health problem as two to three million people, mostly children under 5 years of age, die annually from malaria. Malaria type Duffy represents more than 50 percent of all annual cases of malaria. Fortunately, it is the milder and usually not life-threatening form. Malaria type Duffy is a result of an infection with one of two types of protozoa of the genus Plasmodium (vivax, knowlesi). But malaria is caused also by three other types of parasites: ovale, malariae, and falciparum. The latter is the leading cause of malaria connected mortality as it causes the most severe form of the disease. Despite the fact that malaria can â&#x20AC;&#x153;onlyâ&#x20AC;? cause fever, nausea and flu-like simptoms, do not underestimate any of the types of the disease, because with improper action you can risk serious complications, regardless of the cause.

Bite of a mosquito from genus Anopheles infects us indirectly Plasmodium vivax malaria parasite infects first the female Anopheles mosquito that transmits the infection to humans. Plasmodium then forms a protein called PvDVP that binds to a specific antigen, called Duffy antigen. Such antigens are encountered quite commonly in our red blood cells and they form the Duffy antigen system, which is similar to the AB0 blood group system. Duffy positive people have these antigens, while blood cells of Duffy negative people are absent of these antigens. Plasmodium vivax needs Duffy proteins to enter the red blood cells and subsequently develop the infection. Consequently, Duffy-negative individuals are resistant to malaria. As there are no antigens on the surface of red blood cells, through which the parasite infects them, the infection with this parasite is not possible. The vast majority Caucasians (whites) are Duffypositive and the absence of Duffy antigen is more common in Africans and inhabitants of Papua New Guinea. Probably, at some point in evolution, a mutation occurred, giving people a better chance of survival. People with a mutation were most likely to survive, leading to a retained mutation in the population. Duffy negative heterozygotes are individuals who have twice as little Duffy antigens, since this is in accordance with the genetic makeup of the gene DARC. Heterozygosity does not provide reliable resistance, but still leads to a reduced susceptibility to infection.

Perception of bitter taste Tasting is a process where smell and sight play an important role, but the main organ for tasting is actually the tongue. The tongue is covered with numerous taste buds which contain taste receptors. With their help, we distinguish four basic tastes: sweet, salty, sour and bitter. The ability to taste might not seem as important as good eye sight or hearing, but it does greatly affect the quality of our lives. It affects our decisions when choosing what to have for breakfast. Shall we go to a Chinese or an Italian restaurant? Do we prefer juice, beer, or maybe water? In the civilised world, most people think that taste only serves for culinary experience. But in nature, the distinction between edible and poisonous food is often a matter of life and death both for animals and humans. In this analysis, we examined the gene TAS2R38, which determines that some individuals perceive bitter taste more and some less intensely.

Many people do not detect bitter substances Scientists have determined the ability to taste bitter substances by testing the perception of 6-N-propylthiouracil (PROP) taste. PROP does not exist in nature, but the ability to taste this synthetic substance is similar to tasting other related bitter substances. PROP-related substances are found in broccoli, cabbage, coffee, tonics and some beers. A typical example of such compounds is glucosinolates, but in nature there are thousands of substances with a bitter taste. Humans have about 30 genes that encode receptors for bitter taste, but each of these receptors detects it little differently. Studies have shown that the gene responsible for the difference in bitter taste sensitivity is TAS2R38. About 80 per cent of all people with a common variant of the TAS2R38 gene do not perceive certain bitter tastes.

It is well known that glucosinolates can be toxic because of a negative effect on iodine metabolism. This can lead to thyroid problems and therefore, animals have developed receptors to detect these substances. At some point of our evolution, the ability to taste glucosinolates was no longer relevant due to alterations in diet, so over the course of time the dominant form of the gene TAS2R38 has been preserved.

Your result More intense perception of bitter taste Your genetic analysis has shown that you are a carrier of one common and one altered copy of the gene TAS2R38, which makes you more perceptive to certain bitter tastes. Bitter substances, that you are most likely to taste, can be found in broccoli, kale, chicory, cabbage, spinach and beverages, such as coffee, cocoa, grapefruit juice and some beers. These substances play an important role in digestion, so do not avoid them in your meals just because of bitter taste. If you perceive the taste as truly unpleasant, then we recommend the following: choose younger vegetables, since they are less bitter tasting or prepare the bitter tasting vegetables, by mashing them. The latter will reduce the content of the substances that cause the bitter taste as they are emitted into the descending liquid. Such foods can then be made into soups or prepared with pasta. You can also alleviate the bitter taste by adding your favourite spices to the food.

Alcohol metabolism Your result Efficient alcohol metabolism Your genetic makeup determines an efficient metabolism of alcohol. You are a carrier of the most favourable genetic makeup, and most probably do not have problems with alcohol metabolism and alcohol flush. Your genetic makeup determines that you have no problems with the accumulation of harmful substances from alcohol metabolism. You should not get typical characteristics, such as flushed face, headache, nausea, unpleasant itching and increased heart rate when drinking in moderation. Nevertheless, over-consumption of alcohol does have many negative consequences, both medical as well as sociological, and therefore you are advised to moderate consumption. Despite the efficient metabolism of alcohol, we recommend that you avoid its consumption during and after exercise.

Have you ever wondered why some people have red faces, headache, nausea, and increased heart rate already after consuming very small amounts of alcohol? Alcohol is banned in some populations due to religious reasons, but despite of no religious reasons alcohol consumption is still very rare in some other populations. Some of the peoples tolerate alcohol very poorly, which deters them from drinking. Roughly speaking, we can say that among East-Asians, about half of the population might not be able to tolerate alcohol. It is characteristic for these people to have red faces, headaches, nausea, unpleasant itching and increased heart rate already after consuming small amounts of alcohol. Such problems are rarely encountered among Europeans and Africans, but nevertheless a mutation in some people cannot be excluded.

Scientists have managed to explain the problems in alcohol metabolism also at the molecular level

The main gene responsible for proper alcohol metabolism is encoding the enzyme ALDH2. This enzyme converts the intermediary product of alcohol metabolism, acetaldehyde, into acetic acid. Acetaldehyde is more toxic to our body than ethanol itself, so it is very important that the cellular mechanisms will convert acetaldehyde rapidly further. People, who are carriers of one or two defective copies of the encoding gene, do not typically consume alcohol as it has very negative impact on their wellbeing. Improper functioning of this enzyme prevents a quick removal of acetaldehyde from the cells, making us more sensitive to alcohol and giving us the so-called alcohol flush. Additionally, also another enzyme, called alcohol dehydrogenase (ADH1), is responsible for the alcohol sensitivity by affecting the metabolism of ethanol. This enzyme is responsible for the first step in the metabolism of ethanol to acetaldehyde. ADH1 is an enzyme composed of two subunits, which are encoded by three different genes: ADH1A, ADH1B and ADH1C. Researchers revealed that mutations that take place in these genes affect the efficiency of ethanol conversion. These mutations are not as decisive as those in the ALDH2 gene, but nevertheless largely determine alcohol sensitivity.

Caffeine metabolism Caffeine is a natural alkaloid, which is also the main and most known ingredient of coffee. Caffeine is the most common stimulant in the world, which is found in the leaves, fruits and seeds of many plants. It is mostly extracted from the coffee and cocoa beans, and is also found in tea leaves. It is a mild stimulant that stimulates the central nervous system and the heart, and in addition acts as a weak diuretic accelerating urine excretion. Its effects are psychological (excitement, restlessness, feeling better), as well as physiological (reduced fatigue, faster metabolism, increased blood pressure). However, drinking too much coffee, depending also on the speed of caffeine metabolism, can have a harmful effect on your health. 2 to 3 cups of coffee a day can have a harmful effect on the health of people whose enzyme CYP1A2 does not function efficiently. Such people metabolize caffeine more slowly, which can lead to increased blood pressure issues, so it is important that the doses are adjusted accordingly.

Intense effects of caffeine on the human body are not as favourable as they might seem When you consume coffee, the caffeine is absorbed into the blood in about 5 minutes. The final effect is achieved within 30 minutes and its effect is still evident a few hours after. Caffeine does not accumulate in the body but is decomposed and after about 24 hours excreted from the body. Metabolism or decomposition of caffeine takes place in the liver with an initial de-methylation via an enzyme called cytochrome P4501A2 (CYP1A2). This enzyme is characterized by a great variability of functions, which are partly the result of differences in our genetic makeup. Therefore, changes in our DNA have a significant impact on the efficiency of the enzyme function and thus determine the individual speed of caffeine metabolism.

Scientist have shown by measuring the ratio between plasma and urine and the amount of caffeine metabolites of caffeine after taking a certain amount of coffee, that replacing the 734th nucleotide of CYPI1A2 gene results in reduced enzymatic activity. Coffee has more effect on people who have at least one altered variant of the gene, than on people with two copies of the gene in normal form.

Your result Slow caffeine metabolism The analysis of your genetic makeup revealed one rare and one common copy of the gene CYP1A2, which determines slow caffeine metabolism. About 40 percent of Caucasians have such a genetic makeup and 48 percent of people metabolize caffeine as slowly as you. Because of your genetic makeup, we recommend you not to drink more than one cup of coffee per day as intensified effect of caffeine is not as favourable, as it might seem. As caffeine is metabolized slowly in your body (meaning it retains longer in the body) it can have greater impact on raising your blood pressure. It is therefore not surprising that people who metabolise caffeine more slowly are much more susceptible to problems associated with high blood pressure and are at increased risk for heart attacks. A cup of coffee contains approximately 200 mg of caffeine, a cup of tea 80 mg, and "Coca Cola" somewhere between 40 and 70 mg of caffeine.

Lactose metabolism Your result Ineffective metabolism The analysis of your DNA has shown that you are a carrier of two unfavourable copies of the gene MCM6, which determines an extremely reduced amount or complete absence of the enzyme lactase and consequently results in lactose intolerance. It is very likely that you tolerate a certain degree of lactose despite the unfavourable genetic makeup. Most lactose-intolerant persons can easily consume 8-10 g of lactose per day, some even up to 50 g. However, in highly sensitive people, the lactose consumption must be limited to a maximum of 1 g per day. We recommend that you keep track of your response to lactose intake and see how much lactose you tolerate. In the case of high sensitivity, carefully read the labels of processed meat, margarine, bread, flakes, instant soups and sauces, mixes for biscuits and cakes, because lactose is present also in non-dairy products. We recommend that you adapt for lactose-free milk, where lactose has already been removed. In addition, you can choose also soy or rice milk.

Milk is the first and most important component of food for any baby and child. It has great importance also in the diet of adults with the exception of lactose intolerant people. The latter do not have the enzyme lactase, which is responsible for digestion of milk sugar (lactose), and their milk consumption should therefore be limited. The responsible gene for the absence of the enzyme lactase is the gene named MCM6, which regulates the activity of the gene LCT (gene coding for the enzyme lactase) and thus determines whether we have the lactase enzyme or not. Lactose accumulates in the colon in lactose intolerant people and is then decomposed by intestinal bacteria that produce various fats, gases and other molecules, resulting in diarrhoea, abdominal distension and abdominal cramps. We may also just feel sick and throw up. Symptoms appear between 15 minutes to 2 hours after ingestion of milk or milk products, depending on the amount of lactose that we use, on our age and on our general health condition.

People with two mutated copies of the gene MCM6 almost entirely or completely lack lactase The reason that some people do not experience significant problems is that symptoms depend on age, the amount of lactose and type of lactose consumed (lactose-intolerant people more easily digest yogurt that contains probiotics). The vast majority of people with typical symptoms of lactose intolerance are not even aware of the actual cause of the problem as signs are very non-specific and depend on the above mentioned factors. A medical examination is required for a precise diagnosis. Difficulties in disease detection can arise if the symptoms occur a long time after ingestion of milk and both patient and doctor do not connect them with the inability to metabolise milk. A diagnosis can be achieved through the cessation of milk consumption in the diet. If symptoms disappear after ending milk consumption, then further diagnosis is no longer necessary. However, a lactose intolerance test is available for final confirmation. The test measures the presence of hydrogen in exhaled air after consuming a lactose rich meal and its results match in 90-100 percent with the genotype of the individual.

Episodic memory Human memory is influenced by a number of genes that appear to determine 50 percent of total memory ability. Changes in these genes have major impact on the functioning of our brain and our memory. The ability to memorize is scientifically analysed by presenting large amounts of pictorial and verbal material to people with different genetic background, and then monitoring how many images and words are remembered by individuals with a particular form of a gene. In this way, the importance of the gene KIBRA was discovered. People with a certain variant of the gene were able to remember more words after 5 minutes and 24 hours of presentation than people that did not have this gene variant. Moreover, measurements of brain activity shows that people without the variant of the gene, which determines better memory, require more mental effort for the same tasks.

There are different types of memory

In general, we distinguish short-term and longterm or episodic memory, which is sometimes referred to as autobiographical memory. This type of memory allows us to remember past events that have occurred at a certain time and venue. It enables us to recall information from the distant past, such as the name of a former classmate or the date of an important event. We do not just think of a particular event, but we know how to put it into context. It is this type of memory that is most affected by a variety of brain diseases such as Alzheimerâ&#x20AC;&#x2122;s disease.

It is interesting to observe brain activity while performing tasks that play a role in episodic memory. People with two copies of the most common form of the KIBRA gene are characterized by increased brain activity in areas responsible for memory. This means that they require more effort to perform the same tasks than those who carry at least one rare copy. The exact function of the gene KIBRA in the brain is not completely known, but additional tests have confirmed that motivation or concentration have no effect on memory related research results.

Your result Better episodic memory You are a carrier of one common and one rare copy of the KIBRA gene, so you have better episodic memory compared to people who have two common copies of the gene. About 43 percent of the population has such a genetic makeup as you have. The conclusion was made based on tests, where people with at least one rare copy of the gene could, after five minutes remember written words 24 percent better, and after 24 hours 19 percent better than people with two common copies of the KIBRA gene. One could say that KIBRA provides minor differences in memory abilities among individuals, but there have been cases of people who can remember even the smallest details. Among them is Jill Price, who can describe each day of her life since 14 years of age, with each answer given instantly. However, Jill has often problems, as she simply cannot forget the bad moments, which makes forgetting sometimes advantageous.

Type of earwax Your result You have wet earwax type The genetic analysis has shown that you carry two common copies of the ABCC11 gene. This genetic makeup is most frequent in European population and determines that you have a wet type of earwax. The ABCC11 gene defines the type of earwax. This gene encodes for a protein that belongs to a large family of ABC membrane transporters. ABC transporters consist of a wide variety of proteins, which take care of the transport of molecules across the cell membrane as well as of intracellular membranes. The ABCC11 gene product is specifically involved in the physiological processes of bile acids and conjugated steroids. The normal form of the gene determines the appropriate transport of lipophilic anions, due to which the carriers of at least one normal copy of the ABCC11 gene have a wet type of earwax.

Earwax is an important product of the ear canal, secreted by special ceruminous glands. It is mixed with detached ear canal skin surface cells and its purpose is to protect the ear canal - protect against physical and dust particles, water and insects as well as bacterial and fungal infections. Inadequate secretion of earwax can also cause dry and itchy ears. On the other hand, excessive secretion of wax causes problems because excess ear wax can press against the eardrum and impair hearing. In this case, earwax is removed by gently rinsing the ear canal. This should be done by a doctor because removal with cotton swabs can dangerously damage the eardrum.

Earwax is not only an annoying thing Earwax is usually seen as an annoying thing that accumulates in the ears and has unpleasant appearance. In general two types of earwax, wet and dry are distinguished. Dry wax contains about 20 percent fat, is greyish yellow and has flaky structure. Moist wax on the other hand, contains about 50 percent fat and is either brown or honey colour and is sticky. What type of wax will an individual have, depends largely on the genetic makeup of the gene ABCC11. Most Europeans and Africans have a wet type of earwax, while the majority of Asians have dry earwax. Earwax is produced in the last third of the ear canal. It clears mostly by itself because the wax moves slowly towards the outside, where it dries, forms clumps and falls off. This moving of earwax towards the exterior is quite interesting, because the movement of our jaws helps to transport wax forward.

Learning from mistakes Recently, more and more research is conducted in order to identify the processes in the brain responsible for decision-making. Research revealed that electrical activity occurs in the brain, associated with a specific action before a person realizes that they have actually performed the action. Such findings of physiological studies even put human free will into question. Despite all this, many of our decisions are affected by consequences of our past mistakes - learning from the mistakes and acquiring experience thus helps us in our future decisions. This decision-making process represents a very efficient, but primitive way of learning, observed also in animals. But even with this type of learning, significant differences due to genetic factors are observable in the ability of different people.

Learning from mistakes - the first form of learning

Synapses are narrow gaps between neurons through which biochemical transmitters travel and transmit information between nerve cells. Genetic mechanisms that control the transfer of transmitters, such as dopamine and serotonin, could affect the differences between individualsâ&#x20AC;&#x2122; behaviour and decision-making. Individuals, who have a mutation in the genes that are important for the functioning of these systems, are more susceptible to alcoholism, smoking and obesity.

One of the genes that play an important role is the gene named DRD2 which encodes for dopamine D2 receptor. Certain variants of this gene may impact the decision-making based on an individualâ&#x20AC;&#x2122;s negative past experience. Imaging studies have revealed that the carriers of two rare copies of the gene DRD2 show less activity in the frontal area of the brain when carrying out tasks associated with mistakes committed in the past, and are consequently less effective in learning from mistakes. These people have fewer dopamine receptors, suggesting that dopamine signalling is important for learning from mistakes. This DRD2 gene variant is responsible for a smaller number of binding sites for dopamine in the brain, resulting also in difficulties in quitting smoking and a higher probability for drug use.

Your result More effective learning from mistakes Your analysis of the DRD2 gene, which affects the effectiveness of learning from mistakes, has shown that you carry two favourable copies of the gene, resulting in more effective learning from mistakes. About 65 percent of all people have such a genetic makeup. Among many decisions that we take in life, also knowledge gained from previous mistakes has a great impact. We learn more or less successfully from mistakes and acquire experience, contributing to the fact that in similar situations we would make a right decision. Such decision taking represents a primitive way of learning, present also in animals, but it is actually very effective. This is especially true for you because you have more dopamine receptors in brain, which is important for learning from mistakes. You remember negative consequences from the past well, so in the next similar situation you are likely to choose better.

ANALYSED GENES Gene

Role of the gene

Alzheimerâ&#x20AC;&#x2122;s disease APOE (1)

Apolipoprotein E is important for binding and degradation of lipoprotein particles and cholesterol level regulation. It is correlated to the A-beta factor, which has great influence on the development of Alzheimer's disease.

APOE (2)

CLU CD33

Extracellular chaperon, which prevents aggregation of plasma proteins. It is involved in various biological processes such as cell death, tumor development and the development of neurodegenerative diseases. Protein that is involved in the binding processes of different molecules at the cell surface. High expression of this gene correlates with the development of Alzheimer's disease.

CR1

Gene that encodes the membrane glycoprotein that is found in blood, immune and nerve cells. It is involved in the binding processes of different particles and complexes at the cell surface.

BIN1

Protein that is present in the central nervous system. It represents an important element in the functioning of the nervous system, as it is involved in the processes of endocytosis in nerve synapses.

ABCA7

Protein that belongs to the ABC1 transporters family and is involved in the processes of phagocytosis. The gene is expressed primarily in leukocytes, thymus, spleen and bone marrow.

Asthma ORMDL3

Critical mediator of sphingolipid homeostasis. Unbalanced regulation of sphingolipids leads to the development of asthma in childhood.

Atrial fibrillation PITX2 (1)

The gene is expressed primarily in the pituitary gland and the brain. It regulates the function of genes that are associated with regional and functional specific differentiation of neurons in the brain. It regulates the function of genes which are responsible for the degradation of procollagen.

PITX2 (2)

ZFHX3

Transcription factor, that regulates the differentiation of mioblasts, which are the basic building blocks of muscle.

Coeliac disease HLA-DQA1 (1)

Protein, which binds peptides derived from antigens and presents them on the surface of CD4 T cells for recognition.

IL18RAP

Protein that is part of interleukin 18 (IL-18) receptor and is responsible for binding to the receptor. It is involved in the activation of NF-kappa-B and JNK molecules. In general it is an important part of the immune response.

RGS1

An important regulator that inhibits cellular G-protein signalling pathways. It is also involved in the proliferation and activation of immune B-cells.

CCR1

Receptor for a CC type of chemokines. Chemokines are cytokines which mediate intercellular communication. Chemokines and their receptors represent the key element for transferring the information about the site of infection to the immune effector cells.

IL12A

Cytokine that can act as a growth factor for activated T and NK immune cells. It increases the activity of NK-activated killer cells and stimulates the production of interferon-gamma.

LPP

Protein, that affects the shape, motility and attaching processes of cells. It represents the base around which the complex protein structures in the cytoplasm and in the cell nucleus are formatted.

IL21

Cytokine with important immunoregulatory activity. In association with IL15 and IL18 it stimulates the synthesis of interferon-gamma in T and NK cells. It inhibits the activation and ageing of dendritic cells as well.

TNFAIP3

Protein, that is essential in the ubiquitine repair protein complex, and it ensures the transient nature of inflammatory signalling pathways. It is responsible for the inhibition of programmed cell death.

SH2B3 (1)

The gene is strongly expressed in different cells of the immune system (monocytes and dendritic cells), especially in the case of people with Coeliac disease. The product of this gene has a number of signalling tasks.

Glaucoma ATOH7 SIX1

Transcription factor, that is essential for our vision. It is involved in differentiation of retinal ganglion cells, through which nerve impulses are transmitted in the lateral geniculate nucleus. Gene, that has been found in other organisms to play an important role in the development of the visual system. Genome-wide association studies on human populations have confirmed its role as it has been proven that the gene is involved in the development of glaucoma.

ANALYSED GENES Gene CDKN2B

Role of the gene It is an important regulator of cell proliferation. Researchers believe that through the complex regulation of other genes it influences susceptibility to glaucoma.

CAV1

The exact role of caveolins is still under intense investigation. However, it is known that caveolins are involved in various processes, including the processes necessary to drain fluid from the eye.

LOXL1

Gene, that is important for the development of connective tissues. It encodes extracellular amino oxidase that catalyzes the first step in the formation of cross-fibres in collagen and elastin. Probably together with the FBLN5 and ELN genes, it affects the performance of the eye.

Multiple sclerosis IL7R HLA-DRA (1)

Gene, that encodes the cellular receptor for interleukin 7 (IL-7). IL-7 is important for the proper intracellular communication. Protein that regulates the processes of antigen presentation to CD4 T cells via binding of antigenic peptides.

HLA-B

Protein, that is involved in the processes of presenting foreign antigens to the immune system.

CD58

Protein, that is present on the surface of T lymphocytes. It is important for the T cells immune response regulation.

IL2RA (2)

Interleukin 2, which is an important for proper intracellular communication.

High blood pressure (Hypertension) PLEKHA7 ATP2B1 SH2B3 (2) FGF5 CYP17A1

Gene that is associated with elevated blood pressure and hypertension but its physiological role in pathogenesis is not yet clear. Enzyme that is indirectly involved in the transport of calcium from the cells, through which it affects blood pressure. The gene is strongly expressed in different cells of the immune system (monocytes and dendritic cells), especially in the case of people with Coeliac disease. The product of this gene has a number of signalling tasks. Growth factor that stimulates the growth and proliferation of various cell types, including heart tissue cells and cells of the vascular system of the heart. Enzyme that belongs to the important family of cytochromes. It is involved in the metabolism of progesterone. In genome wide association studies the gene has been shown to be linked with high blood pressure and hypertension.

Psoriasis IL12B HLA-C

Cytokine, that acts as a growth factor for T and NK cells. It increases the lytic activity of NK-activated killer cells and stimulates the production of interferon-gamma. A member of the human leukocyte antigen, which is expressed almost in all cells and is involved in the process of presentation of foreign antigens to the immune system.

IL23R (1)

Protein, that is a part of the IL-23 receptor. It is involved in immune processes by binging IL-23 through the Jet-Stat signal pathway. It stimulates the T and NK cells.

IL23A

This protein is the structural subunit of interleukin-23, that is important in the processes of acquired immunity. It regulates the activity of T and NK immune cells and stimulates the production of inflammatory cytokines. It is often involved in autoimmune diseases and is probably involved in the formation of tumors.

LCE3D

Precursor of the cornified envelope in the outmost layer of the epidermis (stratum corneum).

TNIP1

Although the precise mechanism by which this gene functions is not yet clear, it has been shown through the genome-wide association studies that different variants of this gene are strongly associated with psoriasis.

IL23R (2)

Protein, that is a part of the IL-23 receptor. It is involved in immune processes by binging IL-23 through the Jet-Stat signal pathway. It stimulates the T and NK cells.

Rheumatoid arthritis PTPN22 (1) HLA-DRB1 (1) TNFAIP3 CD40

Intracellular phosphatase that binds to the CBL protein. It is involved in signalling pathways associated with T cell activation. Mutations in this gene are associated with many autoimmune diseases. Protein that binds rheumatoid arthritis-specific autoantibodies and presents them to the CD4 T-cells. One of the members from the superfamily of tumour necrosis factors, which are involved in various inflammatory responses. Receptor from the tumour necrosis factor superfamily. It has a crucial role in the immune and inflammatory response of our body.

ANALYSED GENES Gene

Role of the gene

STAT4

Protein that is involved in immune signalling pathway of IL12 and is also a regulator of transcription.

PADI4

Enzyme that is functionally involved in the production of rheumatoid arthritis-specific autoantibodies.

CD244

Antigen, that modulates interactions between various molecules, which are involved in the leukocyte activation.

Restless leg syndrome MEIS1 BTBD9 MAP2K5 PTPRD

Transcription factor that regulates the expression of PAX6 gene. The latter is an important regulator of the development of the eyes, nose and central nervous system. Gene, for which we don't have a lot of information about its physiological role. The genetic variant in this gene is proven to affect the susceptibility to restless legs syndrome. Gene, which is expressed in many tissues, however the highest level of expression has been detected in skeletal muscle and heart. It plays an important role in the signalling pathway that regulates programmed cell death, survival of nerve cells in and development of vascular system. Protein that belongs to the family of tyrosine phosphatases. It is a signalling molecule important for processes such as cell growth, differentiation and cell division.

2p14

The genetic variant, which is located in the region p14 of chromosome 2. In various studies it has been shown that the genetic variant in combination with MEIS1 gene is associated with restless legs syndrome.

16q12

The genetic variant, which is located in the q12 region of chromosome 16. This variant is associated with the risk for restless legs syndrome.

Diabetes mellitus type 1 HLA-DQA1 (2) INS PTPN22 (1) IL2RA (1) RNLS

Protein, which binds peptides derived from antigens and presents them on the surface of CD4 T cells for recognition. Gene that encodes insulin, which plays an important role in regulating blood sugar. By binding to the receptor, insulin promotes the uptake of glucose from blood to cells and thus it decreases blood sugar levels. Intracellular phosphatase that binds to the CBL protein. It is involved in signalling pathways associated with T cell activation. Mutations in this gene are associated with many autoimmune diseases. Interleukin 2, which is an important for proper intracellular communication. Aminooxidase that is secreted by the kidneys. It decreases heart rate and lowers blood pressure. The gene is also related to the development of diabetes, rheumatoid arthritis and some other autoimmune diseases.

SH2B3 (2)

ERBB3

This protein is receptor for tyrosine kinase. Its activation affects various processes, such as gene expression, cell division and cytoskeleton formation.

CTLA4

Inhibitory receptor, that acts as a negative regulator of T-cell immune response.

CLEC16A

Gene, which encodes calcium-dependent lectins. Polymorphisms in the gene are associated with diabetes, multiple sclerosis and rheumatoid arthritis.

Diabetes mellitus type 2 TCF7L2

Transcription factor, that is important in the regulation of blood sugar.

PPARG

Transcription factor, that has an important influence on the differentiation of fat cells and regulation of blood sugar levels.

HHEX

Transcription factor, that is important for the development of the pancreas, through which it regulates the blood sugar level.

CDKAL1

Gene that is primarily expressed in skeletal muscles and brain. Gene variants affect the expression of the gene which affects the expression of several other genes involved in the regulation of blood sugar level.

SLC30A8

Transporter protein that facilitates the transport of zinc, through which it regulates production and storage of insulin in pancreatic beta cells.

IGFBP2 CDKN2A (2)

Protein that regulates the function of insulin-like growth factors. Changes in the functioning of the gene can result in disrupted sugar metabolism. Kinase, which plays an important role in the regulation of the cell cycle. It effects proliferation and ageing of progenitor cells that are responsible for growth and regeneration of the vascular system.

JAZF1

Nucleus protein, which acts as a regulator of transcription. Mutations in this gene are associated with the development of certain types of tumors.

WFS1

Protein that is involved in the regulation of calcium level in the cells. This is done via through the uptake of calcium in the endoplasmic reticulum.

ANALYSED GENES Gene

Role of the gene

Myocardial infarction (Heart attack) CDKN2A (1) CELSR2 MIA3

Kinase, which plays an important role in the regulation of the cell cycle. It effects proliferation and ageing of progenitor cells that are responsible for growth and regeneration of the vascular system. Receptor from the catherine family, located in the cell membrane. Catherines have a numerous domains, which are thought to represent the receptor sites for communication. The exact role of this protein is not clear yet. However, genome wide association studies have revealed that genetic variants in this gene affect susceptibility to heart attack.

CXCL12

Protein, that is important for the transport of monocytes, macrophages and endothelial cells. It is a key element in the pathogenesis of atherosclerosis. The gene is highly expressed in human arteriosclerotic plaques.

SLC5A3

Inositol transporter. Inositol regulates blood pressure, which could be one of the mechanisms through which heart attacks occurs.

Venous thromboembolism F5 F11 (1) F11 (2)

F5 is an important cofactor involved in blood coagulation. Cofactor is freely present in the blood and is activated by thrombin in blood coagulation processes. Gene, which plays an important role in blood clotting, as it regulates secondary phase of intrinsic path in blood coagulation process. Gene, that plays an important role in blood clotting, as it regulates the secondary phase of the intrinsic path in blood coagulation process.

FGG

The gene for the gamma chain of fibrinogen, which is the basic component of blood clots.

FGA

The gene for the alpha chain of fibrinogen, which is the basic component of blood clots.

FGB

The gene for the beta chain of fibrinogen, which is the basic component of blood clots.

Gallstones ABCG8

Transporter, which has an essential role in the selective transport of cholesterol to and from the enterocytes. It is also essential for the selective extraction of sterols from the liver into the bile.

Skin cancer (Basal-cell carcinoma) PADI6

The enzyme which is responsible for deamination of arginine residues of proteins, which are especially important in the reorganization of the cytoskeleton in the egg and embryo.

RHOU

Protein which mediates cell morphology, cytoskeletal organization, cell proliferation and migration. It stimulates resting cells to re-enter the cell cycle.

TERT (1)

It catalyzes the extension of the 3' ends of chromosome by adding specific telomere repeats. The gene is particularly active in progenitor and cancerous cells.

KRT5

Protein that belongs to a larger family of proteins called keratins. Keratin 5 is produced in special cells of the skin, called keranocites, where it has structural role.

KLF14

Transcription factor, which regulates the expression of genes in embryonic and non-embryonic tissues. Through the regulation of expression it is thought to affect the development of basal cell carcinoma.

SLC45A2

Protein, which is responsible for the differentiation of special skin cells, called melanocytes. This protein regulates the transport of substances, required for the synthesis of melanin. As such it represents an important factor of healthy skin.

TERT (3)

It catalyzes the extension of the 3' ends of chromosome by adding specific telomere repeats. The gene is particularly active in progenitor and cancerous cells.

Lung cancer CHRNA3

A subunit of a nicotine receptor. Nicotine receptors are ion channels in the membranes of neural cells, that regulate the potential of neuron cell membranes. They are the receptors for the nervous transmitter acetylcholine.

TERT (1)

It catalyzes the extension of the 3' ends of chromosome by adding specific telomere repeats. The gene is particularly active in progenitor and cancerous cells.

TERT (2)

It catalyzes the extension of the 3' ends of chromosome by adding specific telomere repeats. The gene is particularly active in progenitor and cancerous cells.

BAG6

A nuclear protein that regulates the processes of cell apoptosis. Mutations in this gene can affect cell pathways, related to programmed cell death, thus promoting tumour growth.

ANALYSED GENES Gene GPC5

Role of the gene Protein that belongs to a group of heparan sulphate proteoglycans. It is located on the surface of cells and plays an important role in the regulation of cell division and growth.

Colorectal cancer POU5F1B

An important gene that affects the prostate cancer susceptibility. It encodes a transcription factor, which is highly expressed in cancerous tissue.

SMAD7

Protein that is an essential component of the signalling pathway of certain group of growth factors. High expression of this gene can induce cell apoptosis.

CRAC1

Genome region that is associated with colorectal cancer. The genetic variant is located in a CRAC1 gene but its role is not clear yet.

11q23

Genetic variant is located on chromosome 11, in q23 region. Mutation at this site of DNA affects the development of colorectal cancer.

EIF3H

Gene that is involved in different initial steps of protein synthesis. Highly expressed gene stimulates the production of proteins and contributes to the establishment of malignant state of cells.

10p14

Genetic variant that is located in the p14 region of chromosome 10. Changes on this part of the DNA affect the development of colorectal cancer.

Breast cancer CASP8

Gene active in apoptotic changes observed in mammalian cells undergoing programmed cell death and therefore influence immune surveillance of malignancies.

FGFR2

Receptor for acidic and basic fibroblast growth factors and has potent mitogenic activity for a wide variety of epithelial cells. Genomic variants are associated susceptibility of familial breast cancer and breast cancer in postmenopausal women.

TNRC9

Gene is differentially expressed in patients who experienced breast cancer relapse to bone versus those who experienced relapse elsewhere in the body.Protects against cell death by inducing antiapoptotic and repressing pro-apoptotic transcripts.

2q35

Common genetic variants of 2q35 chromosome region have been connected to breast cancer susceptibility.

MRPS30

Encoded by nuclear genes and helps in protein synthesis within the mitochondrion. Genomic variants are associated susceptibility of breast cancer in postmenopausal women.

STXBP4

Protein, that is responsible for the transport of vesicles from the cytoplasm to the cell membrane. It is also thought to be responsible for the blood sugar level regulation.

ZNF365 (1) SLC4A7

Overexpression of ZNF365A causes abnormal mitosis during the cell cycle. It is localized to the centrosome throughout the cell cycle in several human cell lines. Transporter protein that regulates intracellular pH and is suggested to have an associated sodium channel activity. Tumor cells have been shown to have an abnormally acidic cytoplasmic pH.

Clopidogrel - prevention of blood clotting CYP2C19 (1)

Protein located in the endoplasmic reticulum and is known to metabolize many xenobiotics, including the anticonvulsive drug mephenytoin, omeprazole, diazepam and some barbiturates.

CYP2C19 (2)

Metformin - regulation of blood sugar C11ORF65 SLC22A1

Gene affects the activity of ATM gene and thus regulates the activity of the AMP-activated protein kinase enzyme (AMPK). Metformin functions via AMPK because AMPK is responsible for the regulation of blood sugar. Polyspecific organic cation transporter in the liver, kidney, and gastrointestinal tract. The transporter has a critical role in the elimination of many endogenous amines as well as a wide array of drugs and environmental toxins.

ANALYSED GENES Gene

Role of the gene

Omeprazole - inhibition of gastric acid secretion CYP2C19 (1) CYP2C19 (2)

Protein located in the endoplasmic reticulum and is known to metabolize many xenobiotics, including the anticonvulsive drug mephenytoin, omeprazole, diazepam and some barbiturates.

Perindopril - treatment of stable coronary artery disease BK1

Protein that has a variety of biological effects on the endothelium and in the peripheral circulation through their action on bradykinin receptor subtypes. Bradykines are peptides that cause blood vessels to dilate (enlarge), and therefore cause blood pressure to lower.

AT1 (1)

Gene for the angiotenzin receptor, that regulates the activity of the angiotenzine II and with that regulates the blood pressure.

AT1 (2)

Gene for the angiotenzin receptor, that regulates the activity of the angiotenzine II and with that regulates the blood pressure.

Statins - lowering blood cholesterol SLCO1B1

Transmembrane protein responsible for the transport of organic anions. Among other things it regulates the disposal of statins in the blood and their intake into liver cells.

Warfarin - prevention of blood clotting CYP2C9 (1)

The enzyme, which is involved in the oxidation of many molecules, such as steroids, fatty acids, and xenobiotics. It is an enzyme that controls the rate of metabolism of warfarin and thus affects the drug concentration in the blood.

CYP2C9 (2) VKORC1

Enzyme that is an important factor in blood clotting as it affects the metabolism of vitamin K. Warfarin operates through this enzyme.

Eye colour HERC2 (2)

Protein, which regulates the production of melanin over tyrosine transport and is reflected in different shades of eyes. The more melanin present in the iris of the eye, the darker the eyes look.

Sensitivity to pain SCN9A

It is involved in the regulation of sodium dependant voltage and permeability of excitable membranes. It plays an important role in the mechanisms of pain sensation, especially in the development of pain caused by inflammation.

Muscle structure ACTN3 PPARalfa

Protein, expressed in the muscles. It binds to actin, and is, therefore, important for muscle contraction. Regulates the expression of genes, responsible for the oxidation fatty acids in the skeletal muscles and the heart muscle.

Nicotine addiction CHRNA5

It is a subunit of a nicotine receptor. Nicotine receptors are ion channels in the membranes of nervous cells, which regulate the potential of neuron cell membranes. They are the receptors for the nervous transmitter acetylcholine.

Resistance to malaria (type Duffy) DARC

It encodes Duffy antigens, which are normally present in red blood cells and form the Duffy antigen system similarly to the AB0 blood type system. Through these antigens human parasites Plasmodium vivax and Plasmodium Knowles enter the cells and cause malaria.

Resistance to infection with noroviruses FUT2

Gene encodes a protein called carbohydrate H type 1, which can be found in the gastrointestinal mucosa and in secretions mucilaginous glands. In 20 per cent of Europeans due to mutations in both copies of the gene FUT2 these proteins cannot be found, so norovirus entry into the body and infection is not possible.

ANALYSED GENES Gene

Role of the gene

Alcohol metabolism ADH1C (1)

ADH1C (2) ADH1B ALDH2

Enzyme involved in the metabolism of countless substrates, such as ethanol, retinol, aliphatic alcohols, hydroxysterols, and products of peroxidation. Its activity, therefore, determines an adequate alcohol metabolism.

Je encim, ki sodeluje v presnovni poti razgradnje alkohola. Odgovoren je za ustrezno presnovo alkohola.

Caffeine metabolism CYP1A2

Enzyme responsible for the breakdown of caffeine, alphatoxin B1 and acetaminophen. It is involved in the synthesis of cholesterol and other lipids.

Lactose metabolism MCM6

Gene that regulates the concentration of the enzyme lactase.

Episodic memory KIBRA

Gene that is expressed in parts of the brain connected with memory functions, such as hippocampus and the temporal lobe.

Type of earwax ABCC1

Protein, which is specifically involved in the physiological processes of bile acids and conjugated steroids. It regulates the transport of lipophilic anions, and a failure of this gene determines a dry type of earwax.

Learning from mistakes DRD2

Dopamine D2 receptor, which represents the binding site for dopamine. It is vital for the process of movement, memory and learning.

Perception of bitter taste TAS2R38

A transmembrane receptor, which determines the ability of detecting bitter substances found in the plant genus Brassica.

SCIENTIFIC SOURCES Alzheimer’s disease Farrer et al . 1997. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA 278(16): 1349-1356 Rubinsztein et al . 1999. Apolipoprotein E genetic variation and Alzheimer’s disease. a meta-analysis. Dement Geriatr Cogn Disord 10(3): 199-209 Harold et al . 2009. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat Genet 41(10): 1088-1093 Jun et al . 2010. Meta-analysis confirms CR1, CLU, and PICALM as alzheimer disease risk loci and reveals interactions with APOE genotypes. Arch Neurol 67(12): 1473-1484 Naj et al . 2011. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. Nat Genet 43(5): 436-441 Hollingworth et al . 2011. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat Genet 43(5): 429-435 Asthma

CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nat Genet 41(7): 776-782 Zhang et al . 2011. Association between the IL7R T244I polymorphism and multiple sclerosis: a meta-analysis. Mol Biol Rep 38(8): 5079-5084 Zivković et al . 2009. The tag SNP for HLA-DRB1*1501, rs3135388, is significantly associated with multiple sclerosis susceptibility: cost-effective high-throughput detection by real-time PCR. Clin Chim Acta 406(1-2): 27-30 De Jager et al . 2009. The role of the CD58 locus in multiple sclerosis. Proc Natl Acad Sci U S A 106(13): 5264-5269 High blood pressure (Hypertension) Newton-Cheh et al . 2009. Genome-wide association study identifies eight loci associated with blood pressure. Nat Genet 41(6): 666-676 Levy et al . 2009. Genome-wide association study of blood pressure and hypertension. Nat Genet 41(6):677-687 Psoriasis

Moffatt et al . 2007. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 448(7152): 470-473

Strange et al . 2010. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet 42(11): 985-990

Atrial fibrillation

Nair et al . 2009. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet 41(2): 199-204

Gudbjartsson et al . 2007. Variants conferring risk of atrial fibrillation on chromosome 4q25. Nature 448(7151): 353-357

Nair et al . 2008. Polymorphisms of the IL12B and IL23R genes are associated with psoriasis. J Invest Dermatol 128(7): 1653-1661

Kääb et al . 2009. Large scale replication and meta-analysis of variants on chromosome 4q25 associated with atrial fibrillation. Eur Heart J 30(7): 813819 Benjamin et al . 2009. Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry. Nat Genet 41(8): 879-881 Gudbjartsson et al . 2009. A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke. Nat Genet 41(8): 876-878 Coeliac disease Dubois et al . 2010. Multiple common variants for celiac disease influencing immune gene expression. Nat Genet 42(4): 295-302 Glaucoma Ramdas et al . 2011. Common genetic variants associated with open-angle glaucoma. Hum Mol Genet 20(12): 2464-2471

Rheumatoid arthritis Stahl et al . 2010. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet 42(6): 508-514 Raychaudhuri et al . 2008. Common variants at CD40 and other loci confer risk of rheumatoid arthritis. Nat Genet 40(10): 1216-1223 Daha et al . 2009. Confirmation of STAT4, IL2/IL21, and CTLA4 polymorphisms in rheumatoid arthritis. Arthritis Rheum 60(5): 1255-1260 Restless leg syndrome Winkelmann et al . 2007. Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet 39(8): 1000-1006 Kemlink et al . 2009. Replication of restless legs syndrome loci in three European populations. J Med Genet 46(5): 315-318

Thorleifsson et al . 2010. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma. Nat Genet 42(10): 906-909

Winkelmann et al . 2011. Genome-wide association study identifies novel restless legs syndrome susceptibility loci on 2p14 and 16q12.1. PLoS Genet 7(7): e1002171

Chen et al . 2010. Ethnicity-based subgroup meta-analysis of the association of LOXL1 polymorphisms with glaucoma. Mol Vis 16: 167-77

Diabetes mellitus type 1

Multiple sclerosis

Burton et al . 2007. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447(7145): 661-678

Hafler et al . 2007. Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med 357(9): 851-862

Todd et al . 2007. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat Genet 39(7): 857-864

De Jager et al . 2009. Meta-analysis of genome scans and replication identify

Qu et al . 2010. In silico replication of the genome-wide association results of the Type 1 Diabetes Genetics Consortium. Hum Mol Genet 19(12): 2534-2538

Qu et al . 2007. Toward further mapping of the association between the IL2RA locus and type 1 diabetes. Diabetes 56(4): 1174-1176 Barrett et al . 2009. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 41(6): 703-707 Smyth et al . 2008. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med 359(26): 2767-2777 Kavvoura et al . 2005. CTLA-4 gene polymorphisms and susceptibility to type 1 diabetes mellitus: a HuGE Review and meta-analysis. Am J Epidemiol 162(1): 3-16 Hakonarson et al . 2007. A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene. Nature 448(7153): 591-594

carcinoma. Nat Genet. 41(8): 909-914 Rafnar et al . 2009. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet 41(2): 221-227 Lung cancer Hung et al . 2008. A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature 452(7187): 633-637 Liu et al . 2010. A second genetic variant on chromosome 15q24-25.1 associates with lung cancer. Cancer Res 70(8): 3128-3135 Amos et al . 2008. Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet 40(5): 616-622

Diabetes mellitus type 2

Thorgeirsson et al . 2008. A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature 452(7187): 638-642

Scott et al . 2007. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316(5829): 1341-1345

Rafnar et al . 2009. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet 41(2): 221-227

Zeggini et al . 2007. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316(5829): 1336-1341

Wang et al . 2008. Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat Genet 40(12): 1407-1409

Zeggini et al . 2008. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet 40(5): 638-645

Li et al . 2010. Genetic variants and risk of lung cancer in never smokers: a genome-wide association study. Lancet Oncol 11(4): 321-330

Sandhu et al . 2007. Common variants in WFS1 confer risk of type 2 diabetes. Nat Genet 39(8):951-953 Franks et al . 2008. Replication of the association between variants in WFS1 and risk of type 2 diabetes in European populations. Diabetologia 51(3): 458463 Myocardial infarction (Heart attack) Kathiresan et al . 2009. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet 41(3): 334-341 Venous thromboembolism Segal et al . 2009. Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review. JAMA 301(23): 2472-2485 Smith et al . 2007. Association of genetic variations with nonfatal venous thrombosis in postmenopausal women. JAMA 297(5):489-498

McKay et al . 2008. Lung cancer susceptibility locus at 5p15.33. Nat Genet 40(12): 1404-1406 Hoppenbrouwers et al . 2009. Replication of CD58 and CLEC16A as genomewide significant risk genes for multiple sclerosis. J Hum Genet 54(11): 676-680 Colorectal cancer Tomlinson et al . 2007. A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat Genet 39(8): 984988 Tomlinson et al . 2008. A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3. Nat Genet 40(5): 623-630 Broderick et al . 2007. A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk. Nat Genet 39(11): 1315-1317 He et al . 2011. Generalizability and epidemiologic characterization of eleven colorectal cancer GWAS hits in multiple populations. Cancer Epidemiol Biomarkers Prev 20(1): 70-81

Arellano et al . 2010. Gene variants associated with venous thrombosis: confirmation in the MEGA study. J Thromb Haemost 8(5): 1132-1134

Tenesa et al . 2008. Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21. Nat Genet 40(5): 631-637

Gallstones

Pittman et al . 2008. Refinement of the basis and impact of common 11q23.1 variation to the risk of developing colorectal cancer. Hum Mol Genet 17(23): 3720-3727

Buch et al . 2007. A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease. Nat Genet 39(8): 995-999

von Holst et al . 2010. Association studies on 11 published colorectal cancer risk loci. Br J Cancer 103(4): 575-5780

Skin cancer (Basal-cell carcinoma)

Breast cancer

Stacey et al . 2008. Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits. Nat Genet 40(11): 1313-1318

Cox et al . 2007. A common coding variant in CASP8 is associated with breast cancer risk. Nat Genet 39(3): 352-358

Stacey et al . 2009. New common variants affecting susceptibility to basal cell

Sergentanis et al . 2010. Association of two CASP8 polymorphisms with breast cancer risk: a meta-analysis. Breast Cancer Res Treat 120(1): 229-234

SCIENTIFIC SOURCES Easton et al . 2007. Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447(7148): 1087-1093 Zhang et al . 2010. Current evidence on the relationship between three polymorphisms in the FGFR2 gene and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 124(2): 419-424 Stacey et al . 2007. Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet 39(7): 865-869 Milne et al . 2009. Risk of estrogen receptor-positive and -negative breast cancer and single-nucleotide polymorphism 2q35-rs13387042. J Natl Cancer Inst 101(14): 1012-1018 Stacey et al . 2008. Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet 40(6): 703-706 Milne et al . 2010. Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study. Breast Cancer Res 12(6): R110 Turnbull et al . 2010. Genome-wide association study identifies five new breast cancer susceptibility loci. Nat Genet 42(6): 504-507 Clopidogrel - prevention of blood clotting Scott et al . 2011. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy. Clin Pharmacol Ther 90(2): 328-332 Yin et al . 2011. Pharmacogenomics of clopidogrel: evidence and perspectives. Thromb Res 128(4): 307-316 Mega et al . 2010. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA 304(16): 1821-1830 Jin et al . 2011. Cytochrome P450 2C19 polymorphism is associated with poor clinical outcomes in coronary artery disease patients treated with clopidogrel. Mol Biol Rep 38(3): 1697-1702

Zhao et al . 2008. Effect of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple therapy for Helicobacter pylori eradication: a meta-analysis. Helicobacter 13(6): 532-541 Ando et al . 2008. Endoscopic analysis of gastric ulcer after one weekâ&#x20AC;&#x2122;s treatment with omeprazole and rabeprazole in relation to CYP2C19 genotype. Dig Dis Sci 53(4): 933-937 Klotz et al . 2005. CYP2C19 polymorphism and proton pump inhibitors. Basic Clin Pharmacol Toxicol 95(1): 2-8 Lehmann et al . 2003. Polymorphisms and the pocketbook: the costeffectiveness of cytochrome P450 2C19 genotyping in the eradication of Helicobacter pylori infection associated with duodenal ulcer. J Clin Pharmacol 43(12): 1316-1323 Perindopril - treatment of stable coronary artery disease Brugts et al . 2010. Genetic determinants of treatment benefit of the angiotensin-converting enzyme-inhibitor perindopril in patients with stable coronary artery disease. Eur Heart J 31(15): 1854-1864 Brugts et al . 2010. Tailored therapy of ACE inhibitors in stable coronary artery disease: pharmacogenetic profiling of treatment benefit. Pharmacogenomics 11(8): 1115-1126 Denus 2010. Pharmacogenomic testing for angiotensin-converting enzyme inhibitors: getting ready for prime time. Pharmacogenomics 11(10): 13451348 Statins - lowering blood cholesterol Niemi 2010. Transporter pharmacogenetics and statin toxicity. Clin Pharmacol Ther 87(1): 130-133 Link et al . 2008. SLCO1B1 variants and statin-induced myopathy--a genomewide study. N Engl J Med 359(8): 789-799 Maggo et al . 2011. Clinical implications of pharmacogenetic variation on the effects of statins. Drug Saf 34(1): 1-19 Warfarin - prevention of blood clotting

Damani et al . 2010. The case for routine genotyping in dual-antiplatelet therapy. J Am Coll Cardiol 56(2): 109-111

International Warfarin Pharmacogenetics Consortium 2009. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med 360(8): 753-764

Metformin - regulation of blood sugar

Mahajan et al . 2011. Clinical applications of pharmacogenomics guided warfarin dosing. Int J Clin Pharm 33(1): 10-19

GoDARTS and UKPDS Diabetes Pharmacogenetics Study Group 2011. Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. Nat Genet 43(2): 117-120 Brecker et al . 2009. Genetic variation in the organic cation transporter 1 is associated with metformin response in patients with diabetes mellitus. Pharmacogenomics J 9(4): 242-247

Takeuchi et al . 2009. A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose. PLoS Genet 5(3): e1000433 Lenzini et al . 2010. Integration of genetic, clinical, and INR data to refine warfarin dosing. Clin Pharmacol Ther 87(5): 572-578

Becker et al . 2009. Genetic variation in the multidrug and toxin extrusion 1 transporter protein influences the glucose-lowering effect of metformin in patients with diabetes: a preliminary study. Diabetes 58(3): 745-749

Epstein et al . 2010. Warfarin genotyping reduces hospitalization rates results from the MM-WES (Medco-Mayo Warfarin Effectiveness study). J Am Coll Cardiol 55(25): 2804-2812

Omeprazole - inhibition of gastric acid secretion

Eye colour

Saitoh et al . 2009. Influences of CYP2C19 polymorphism on recurrence of reflux esophagitis during proton pump inhibitor maintenance therapy. Hepatogastroenterology 56(91-92): 703-706

Sturm et al . 2008. A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color. Am J Hum Genet 82(2): 424-431

Kayser et al . 2008. Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene. Am J Hum Genet 82(2): 411-423

Caffeine metabolism Palatini et al . 2009. CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension. J Hypertens 27(8): 1594-1601

Sensitivity to pain

Cornelis et al . 2006. Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA 295(10): 1135-1141

Reimann et al . 2010. Pain perception is altered by a nucleotide polymorphism in SCN9A. Proc Natl Acad Sci USA 107(11): 5148-5153

Lactose metabolism

Muscle structure

Bersaglieri et al . 2004. Genetic signatures of strong recent positive selection at the lactase gene. Am J Hum Genet 74(6): 1111-1120

Yang et al . 2003. ACTN3 genotype is associated with human elite athletic performance. Am J Hum Genet 73(3): 627-631

Enattah et al . 2002. Identification of a variant associated with adult-type hypolactasia. Nat Genet 30(2): 233-237

Ahmetov et al . 2006. PPARalpha gene variation and physical performance in Russian athletes. Eur J Appl Physiol 97(1): 103-108

Episodic memory

Nicotine addiction

Papassotiropoulos et al . 2006. Common Kibra alleles are associated with human memory performance. Science 314(5798): 475-478

Thorgeirsson et al . 2008. A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature 452(7187): 638-642

Type of earwax

Liu et al . 2010. Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nat Genet 42(5): 436-440 Thorgeirsson et al . 2010. Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. Nat Genet 42(5): 448-453 Resistance to infection with noroviruses Kindberg et al . 2007. Host genetic resistance to symptomatic norovirus (GGII.4) infections in Denmark. J Clin Microbiol 45(8): 2720-2720 Thorven et al . 2005. A homozygous nonsense mutation (428G-->A) in the human secretor (FUT2) gene provides resistance to symptomatic norovirus (GGII) infections. J Virol 79(24): 15351-15355 Resistance to malaria (type Duffy) Grimberg et al . 2007. Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein. PLoS Med 4(12): e337 Tournamille et al . 1995. Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals. Nat Genet 10(2): 224-228 Baldness Richards et al . 2008. Male-pattern baldness susceptibility locus at 20p11. Nat Genet 40(11): 1282-1284 Alcohol metabolism Yokoyama et al . 2005. Hangover susceptibility in relation to aldehyde dehydrogenase-2 genotype, alcohol flushing, and mean corpuscular volume in Japanese workers. Alcohol Clin Exp Res 29(7): 1165-1171 MartĂnez et al . 2010. Variability in ethanol biodisposition in whites is modulated by polymorphisms in the ADH1B and ADH1C genes. Hepatology 51(2): 491-500

Yoshiura et al . 2006. A SNP in the ABCC11 gene is the determinant of human earwax type. Nat Genet 38(3): 324-330 Learning from mistakes Klein et al . 2007. Genetically determined differences in learning from errors. Science 318(5856): 1642-1645 Perception of bitter taste Timpson et al . 2007. Refining associations between TAS2R38 diplotypes and the 6-n-propylthiouracil (PROP) taste test: findings from the Avon Longitudinal Study of Parents and Children. BMC Genet 8: 51