DNA TEST - ADHD SENSOR

Page 1

ADHD Sensor Muster Musterkind DEMO_DNAMEDIC

COVER LETTER

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ADHD Sensor

3HUVRQDO DQDO\VLV UHVXOWV IRU

Muster Musterkind | Date of birth: 01/01/2004 2UGHU QXPEHU

DEMO_DNAMEDIC

Table of contents General Information Attention deficit-hyperactivity disorder

1

Value of a genetic test Part 1 – Genetic risk

4

Part 2 – Other risk

7

Part 3 – The best medication

11

Technical information about ADHD medication

26

General Information References

34

Technical details

33

This report contains personal genetic data and is to be treated confidentially.

OR

T O

$WWHQWLRQ GHILFLW K\SHUDFWLYLW\ GLVRUGHU Attention deficit-hyperactivity disorder ADHD is a disorder hereby children either have significant difficulties in maintaining attention and/or suffer from hyperactivity and impulsiveness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The predominantly inattentive type

:

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The predominantly hyperactive impulsive type 6 : ➤ )LGJHW DQG VTXLUP LQ WKHLU VHDWV ➤ 7DON QRQVWRS ➤ 'DVK DURXQG WRXFKLQJ RU SOD\LQJ ZLWK DQ\WKLQJ DQG HYHU\WKLQJ LQ VLJKW ➤ +DYH WURXEOH VLWWLQJ VWLOO GXULQJ GLQQHU VFKRRO DQG VWRU\ WLPH ➤ %H FRQVWDQWO\ LQ PRWLRQ ➤ +DYH GLIILFXOW\ GRLQJ TXLHW WDVNV RU DFWLYLWLHV ➤ DQG DOVR WKHVH PDQLIHVWDWLRQV SULPDULO\ RI LPSXOVLYLW\ > @ ➤ %H YHU\ LPSDWLHQW ➤ %OXUW RXW LQDSSURSULDWH FRPPHQWV VKRZ WKHLU HPRWLRQV ZLWKRXW UHVWUDLQW DQG DFW ZLWKRXW UHJDUG IRU FRQVHTXHQFHV ➤ +DYH GLIILFXOW\ ZDLWLQJ IRU WKLQJV WKH\ ZDQW RU ZDLWLQJ WKHLU WXUQV LQ JDPHV

The genetics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9DOXH RI D JHQHWLF WHVW Genetic testing has 3 ma or areas of benefit for the diagnosis treatment and management of the disorder. 7KLV JHQHWLF WHVW DQDO\VHG WKH UHOHYDQW JHQHV WR FRYHU DOO UHOHYDQW DUHDV IRU $'+'

Part 1 – Genetic risk +RZ KLJK LV WKH JHQHWLF ULVN RI GHYHORSLQJ $'+'"

Part 2 – Other risk ,I $'+' KDV GHYHORSHG LV WKHUH DQ LQFUHDVHG ULVN RI GHYHORSLQJ RWKHU GLVRUGHUV"

Part 3 – The best medication :KDW LV WKH EHVW PHGLFDWLRQ IRU WUHDWLQJ WKH GLVRUGHU" :KLFK GUXJV ZLOO QRW ZRUN RU FDXVH GDQJHURXV VLGH HIIHFWV" 7KH IROORZLQJ SDJHV ZLOO FRYHU HDFK RI WKHVH DUHDV LQ WXUQ

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E ET C R

3DUW ± *HQHWLF ULVN Genetics play a role in the development of ADHD in appro imately 7 of all cases. This strong genetic component makes people ith unfortunate genetic variants more likely to develop the disorder and helps ith diagnosing suspected cases of ADHD. 6WLOO RI DOO $'+' FDVHV GR QRW FDUU\ JHQHWLF YDULDQWV WKDW SUHGLVSRVH WKHP WR WKH GLVRUGHU > @ VR WKLV VHFWLRQ VKRXOG EH VHHQ DV SURYLGLQJ SRVVLEOH FRQILUPDWLRQ IRU VXVSHFWHG FDVHV WKDW DOUHDG\ VKRZ D QXPEHU RI V\PSWRPV ,W VKRXOG QRW EH VHHQ DV D GHILQLWH GLDJQRVLV RI FKLOGUHQ ZLWKRXW DQ\ V\PSWRPV RI $'+' 2Q WKH IROORZLQJ SDJH \RX ZLOO ILQG D VXPPDU\ RI WKH UHOHYDQW JHQH DQG WKH YDULDQWV WKDW ZHUH DQDO\VHG

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ADHD gene 1 Dopamine transp. S C6A3 Dat1 :KHQ D QHUYH LPSXOVH PRYHV IURP RQH EUDLQ FHOO WR WKH QH[W WKH ILUVW EUDLQ FHOO UHOHDVHV D FKHPLFDO GRSDPLQH LQWR WKH VSDFH EHWZHHQ WKH WZR GLIIHUHQW FHOOV WKH V\QDSVHV 7KH VHFRQG EUDLQ FHOO UHFRJQL]HV WKLV FKHPLFDO DQG FUHDWHV D QHUYH LPSXOVH WKDW LW WKHQ SDVVHV RQ WR WKH QH[W FHOO LQ WKH VDPH FKHPLFDO UHOHDVLQJ ZD\ 7KLV ZD\ DQ LPSXOVH FDQ MXPS IURP RQH FHOO WR WKH QH[W WKHUHE\ SDVVLQJ WKURXJK WKH EUDLQ DQG FRQWUROOLQJ YDULRXV DVSHFWV RI RXU PLQG DQG ERG\ $IWHU RQH FHOO KDV UHOHDVHG WKH FKHPLFDO IRU WKH RWKHU FHOO LW QHHGV WR DEVRUE WKH FKHPLFDO DJDLQ LQ RUGHU WR EH UHDG\ IRU WKH QH[W LPSXOVH 7KLV LV H[DFWO\ ZKDW WKH $'+' JHQH GRHV ,W DEVRUEV WKH FKHPLFDO DQG PRYHV LW EDFN WR WKH FHOO IRU WKH QH[W QHUYH LPSXOVH > @ *HQHWLF YDULDQWV FDQ PRGLI\ WKH HIIHFWLYHQHVV E\ ZKLFK WKH $'+' JHQH FDQ SHUIRUP WKLV IXQFWLRQ $Q\ UHGXFWLRQ LQ IXQFWLRQ FDQ OHDG WR D QXPEHU RI GLIIHUHQW QHXURORJLFDO UREOHPV VXFK DV $'+' > @

The relevant genetic variants in the ADHD genes 1 and 2 ADHD gene 1 - DAT1

Result

Variant 1 - rs27072

C/C

Variant 2 - 40 bp repeat

R/ R

-

Result

Conse uence

ADHD gene 2 - COMT Variant 1 - rs46 0 Val1

Met

Conse uence RIS

A/A

RIS

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Medical conse uence Risk of developing ADHD 11-16 NORMA RIS

HIGH RIS

â–²

Typical severity of symptoms 17 MI D

SEVERE

â–²

Results Summary ➤ $ GLVHDVH FDXVLQJ JHQHWLF YDULDQW KDV EHHQ LGHQWLILHG 7KH ULVN RI $'+' LV WKHUHIRUH VLJQLILFDQWO\ LQFUHDVHG > @ ➤ ,Q DGGLWLRQ RQH JHQHWLF YDULDQW &207 FDXVHV WKH V\PSWRPV WR W\SLFDOO\ EH PRUH VHYHUH WKDQ LQ FDUULHUV RI RWKHU JHQHWLF YDULDQWV > @

Medical conse uence ➤ ,I WKH SDWLHQW DOVR H[KLELWV W\SLFDO V\PSWRPV OHDGLQJ WR D VXVSHFWHG GLDJQRVLV RI $'+' WKLV DQDO\VLV IXUWKHU FRQILUPV WKH GLDJQRVLV > @

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E ET C R

3DUW ± 2WKHU 5LVN The combination of ADHD and certain genetic variants can also increase the risk of other psychological disorders or symptoms. %\ DQDO\VLQJ WKH UHOHYDQW JHQHV ZH FDQ SUHGLFW WKH ULVN RI RWKHU FRPSOLFDWLRQV IURP DULVLQJ DQG HQDEOLQJ \RX DQG \RXU FOLQLFLDQ WR FRXQWHUDFW DSSURSULDWHO\ 2Q WKH IROORZLQJ SDJH \RX ZLOO ILQG D VXPPDU\ RI WKH UHOHYDQW JHQH DQG WKH YDULDQWV WKDW ZHUH DQDO\VHG

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ADHD gene 2 COMT Val1

Met

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ADHD gene 3 OPRM1 7KH RSRLG UHFHSWRU PX $'+' JHQH SURGXFHV D UHFHSWRU LQ FHUWDLQ EUDLQ FHOOV WKDW LV NQRZQ WR PRGLI\ WKH ULVN RI DGGLFWLRQ WR DOFRKRO QLFRWLQH RU LOOHJDO GUXJV > @ 3HRSOH FDUU\LQJ FHUWDLQ JHQHWLF YDULDQWV DUH DW DQ LQFUHDVHG ULVN RI GHSHQGHQFH RQ WKHVH VXEVWDQFHV DQG VKRXOG WDNH SUHYHQWLYH PHDVXUHV WR PLQLPL]H FRQWDFW WR VXFK VXEVWDQFHV

The relevant genetic variants in the ADHD genes 2 and 3 ADHD gene 2 - COMT Variant 1 - rs46 0 Val1

Met

ADHD gene 3 OPRM1 Variant 1 - rs17

71 Asn40Asp

Result

Conse uence

A/A

-

Result

Conse uence

A/A

-

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Medical conse uence ikely type of ADHD 20 INATTENTIVE T PE

H PERACTIVE T PE

▲

Adolescent canabis use: risk of schi ophrenia 21 NORMA RIS

HIGH RIS

11-fold

▲

eeling of re ard / happiness at pleasent events 22 2 AS HIGH

NORMA

▲

ikelihood of agressive antisocial behaviour ith ADHD 23-26 NORMA

I E

HOOD

3 AS I E

▲

Risk of alcoholism and drug addiction 27 NORMA

HIGHER

▲

Page 9 of 38

Results Summary ➤ 7KH JHQHWLF YDULDQW LQ WKH &207 JHQH SUHGLVSRVHV WKH SDWLHQW WR WKH LQDWWHQWLYH W\SH RI $'+' LQVWHDG RI WKH K\SHUDFWLYH LPSXOVLYH W\SH > @ ➤ 3HRSOH FDUU\LQJ WKLV JHQHWLF YDULDQW W\SLFDOO\ KDYH D [ KLJKHU IHHOLQJ RI UHZDUG DQG DOVR H[SHULHQFH SOHDVDQW HYHQWV DSSUR[LPDWHO\ WZLFH DV SOHDVDQW DV RWKHU JHQHWLF W\SHV GR > @ ➤ 7KH JHQHWLF YDULDQW LQ WKH 2350 JHQH GRHV QRW LQFUHDVH WKH ULVN RI VXEVWDQFH DGGLFWLRQ > @

Page 10 of 38

R

CO E ET C

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The path of drugs through our body

drug is taken Drug sho s effect

en yme gene

drug is prepared for breakdo n by en yme

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drug enters urine

Page 11 of 38

ong-term Drug Treatment 'XH WR WKH IDFW WKDW PDQ\ GUXJV RSHUDWH RYHU D ORQJ SHULRG RI WLPH WKH\ QHHG WR EH WDNHQ LQ UHJXODU LQWHUYDOV WR HQVXUH WKDW WKH DPRXQW RI WKH GUXJ LQ WKH EORRGVWUHDP LV NHSW LQ WKH FRUUHFW UDQJH

administration

Drug in blood active range of drug

0h

h

16h

24h

32h

Time hours 7KLV LV KRZ WKH GUXJ DOZD\V UHPDLQV DW WKH ULJKW FRQFHQWUDWLRQ DQG VKRZV LWV LQWHQGHG HIIHFW

Genetic defects inhibit the break do n of the drug 8QIRUWXQDWHO\ PDQ\ SHRSOH FDUU\ D GHIHFW LQ RQH RI WKH HQ]\PH SURGXFLQJ JHQHV WKDW DUH FUXFLDO LQ WKLV SURFHVV

drug is taken

Drug sho s effect

en yme gene

drug is not filtered out of bloodstream

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Page 12 of 38

The problem ith regular administration of a drug hen there is a genetic defect ,Q WKH FDVH RI EORRG WKLQQHUV GUXJ DFWLRQ LV DW WKH ULJKW OHYHO LQ WKH EHJLQQLQJ RI WKHUDS\ EXW WKH FRQFHQWUDWLRQ RI WKH GUXJ ULVHV FRQVWDQWO\ ZLWK HYHU\ DGPLQLVWUDWLRQ XQWLO LW UHDFKHV WR WKH SRLQW RI FDXVLQJ XQFRQWUROOHG EOHHGLQJ

genetic defect slo s breakdo n of drug

to ic concentration adverse reactions

administration Drug in blood

active range of drug

0h

h

16h Time hours

24h

32h

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Page 13 of 38

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drug is taken

en yme gene

Drug is activated by en yme Drug sho s effect

drug enters urine

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drug is taken Drug sho s no effect

en yme gene

Drug is not activated

drug is not filtered out of bloodstream

Page 14 of 38

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Recommended dosage: 100 7KLV LV WKH QRUPDO VWDWH ZKHQ WKH UHOHYDQW JHQHV GR QRW FRQWDLQ DQ\ SHUIRUPDQFH UHGXFLQJ JHQH YDULDWLRQV $GPLQLVWUDWH WKH PHGLFDWLRQ DV XVXDO

Recommended dosage: 20

0

70

etc.

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Recommended dosage: 0 7KH HQ]\PHV LQYROYHG LQ WKH DEVRUSWLRQ RI WKLV PHGLFDWLRQ KDYH OLPLWHG IXQFWLRQ DQG WKH DEVRUSWLRQ UDWH LV SUREDEO\ YHU\ ORZ $OWHUQDWLYH FRPSRXQGV ZLOO PRVW OLNHO\ EH PRUH HIIHFWLYH ,I DEVROXWHO\ QHFHVVDU\ XVH WKLV GUXJ ZLWK FORVH VXUYHLOODQFH IRU HIIHFWLYHQHVV DQG VLGH HIIHFWV

Page 15 of 38

ADHD gene 4 ADRA2A rs1 00 44 7KH $'+' JHQH LV LQYROYHG LQ WKH UHOHDVH RI WKH FKHPLFDOV QHXURWUDQVPLWWHUV WKDW HQDEOH RQH EUDLQ FHOO WR VLJQDO WR DQRWKHU EUDLQ FHOO DQG WKHUHE\ SDVV RQ D QHUYH LPSXOVH &HUWDLQ JHQHWLF YDULDQWV KDYH GLIIHUHQW HIIHFWV RQ WKH DFWLYLW\ RI WKLV JHQH DQG VFLHQWLILF UHVHDUFK KDV VKRZQ WKDW FHUWDLQ JHQHWLF W\SHV UHVSRQGHG YHU\ ZHOO WR 0HWK\OSKHQLGDWH HJ 5LWDOLQ DV D SRVVLEOH WUHDWPHQW RSWLRQ IRU $'+' > @

ADHD gene 2 COMT Val1

Met

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> @

ADHD gene

C P2D6 – common variants

$'+' JHQH FUHDWHV D OLYHU HQ]\PH WKDW LV UHVSRQVLEOH IRU WKH EUHDNGRZQ DQG HOLPLQDWLRQ RI PRUH WKDQ RI FXUUHQWO\ SUHVFULEHG GUXJV IURP WKH ERG\ ,I WKLV JHQH LV GHIHFWLYH WKH GUXJV LQFOXGLQJ DPSKHWDPLQHV $WRPH[HWLQH DQG 0HWKR[\DPSKHWDPLQH PD\ EH HOLPLQDWHG IURP WKH ERG\ DW D VORZHU UDWH DQG FDXVH VHYHUH VLGH HIIHFWV LI WDNHQ RYHU ORQJ SHULRGV 'UXJV WKDW DUH PHWDEROLVHG DQG EURNHQ GRZQ E\ WKLV HQ]\PH VKRXOG EH WDNHQ DW VLJQLILFDQWO\ ORZHU GRVDJHV LI QR DOWHUQDWLYH GUXJV FDQ EH XVHG LQ RUGHU WR SUHYHQW VLGH HIIHFWV > @ 7KHUH DUH FRPPRQ JHQHWLF GHIHFWV LQ WKLV JHQH DOO RI ZKLFK GLVUXSW WKH IXQFWLRQ DQG FDXVH WKH UHOHYDQW $'+' PHGLFDWLRQ OHYHOV LQ WKH EORRG WR EH DEQRUPDOO\ KLJK 6KRXOG DQ\ RI WKHVH JHQHWLF GHIHFWV EH SUHVHQW ZKLFK LV WKH FDVH LQ PRUH WKDQ RI WKH SRSXODWLRQ WKH GRVDJHV RI DPSKHWDPLQHV $WRPH[HWLQH DQG 0HWKR[\DPSKHWDPLQH VKRXOG EH VLJQLILFDQWO\ UHGXFHG > @

ADHD gene 1 Dopamine transp. S C6A3 Dat1 7KLV 'RSDPLQH WUDQVSRUWHU JHQH KDV EHHQ VKRZQ WR DIIHFW WKH HIIHFWLYHQHVV RI WKH GUXJ 0HWK\OSKHQLGDWH 5LWDOLQ LI FHUWDLQ JHQHWLF YDULDQWV DUH SUHVHQW 7KH HIIHFW RI D JHQHWLF YDULDQW LV YHU\ YDULDEOH IURP SHUVRQ WR SHUVRQ VR LW LV SRVVLEOH WKDW VRPH SDWLHQW UHVSRQGV EHWWHU WR WKH GUXJ DQG RWKHUV UHVSRQG OHVV ZHOO WR WKH GUXJ > @

Page 16 of 38

ADHD gene 1 - DAT1 32

Result

Variant 2 - 40 bp repeat

R/ R

Conse uence RIS

ADHD gene 2 - COMT Variant 1 - rs46 0 Val1

Result Met

Conse uence

A/A

2 -30

RIS

ADHD gene 4 - ADRA2A

Result

Variant 1 - rs1 00 44 2

C/G

Conse uence RIS

Drug Category 1

polymorphism

of gene condition

drug metabolism

Cytochrome P-4 0 2D6

2 4 A/del Allele 3

active

rapid

Cytochrome P-4 0 2D6

1 46 G/A Allele 4

inactive

Cytochrome P-4 0 2D6

1707 T/del Allele 6

active

rapid

Cytochrome P-4 0 2D6

2 3 A/C Allele 7

active

rapid

Cytochrome P-4 0 2D6

17 G/T Allele /14

active

rapid

TRA RAPID META O I ER

slo

E TENSIVE META O I ER

INTERMEDIATE META O I ER

our result

polymorphism

of gene condition

drug metabolism

Cytochrome P-4 0 2C

Arg144Cys Allele 2

active

rapid

Cytochrome P-4 0 2C

Ile3

eu Allele 3

active

rapid

O I ER POOR META

Drug Category 2

TRA RAPID META O I ER

E TENSIVE META O I ER

INTERMEDIATE META O I ER

O I ER POOR META

our result

Drug Category 3 Cytochrome P-4 0 2C1 TRA RAPID META O I ER

polymorphism

of gene condition

drug metabolism

6 1 G/A Allele 2

active

rapid

E TENSIVE META O I ER

INTERMEDIATE META O I ER

O I ER POOR META

our result

Drug Category Cytochrome P-4 0 3A4 TRA RAPID META O I ER

polymorphism rs2 3717 Allele 1 E TENSIVE META O I ER

of gene condition

drug metabolism

active

rapid

INTERMEDIATE META O I ER

O I ER POOR META

our result

Drug Category 6 Cytochrome P-4 0 3A TRA RAPID META O I ER

polymorphism

of gene condition

rs776746 Allele 1

inactive

O I ER RAPID META

slo

E TENSIVE META O I ER

drug metabolism

O I ER POOR META

our result

Drug Category 7

polymorphism

of gene condition

drug metabolism

P-4 0 2E1 Cytochrome

rs72 710 Allele 2

active

rapid

TRA RAPID META O I ER

E TENSIVE META O I ER our result

INTERMEDIATE META O I ER

O I ER POOR META

Page 17 of 38

Drug Category

polymorphism

P-4 0 1A2 Cytochrome

rs206 14

P-4 0 1A2 Cytochrome

rs762 1

TRA RAPID META O I ER

1C 1

E TENSIVE META O I ER our result

of gene condition

drug metabolism

inhibited

inhibited

active

very rapid

INTERMEDIATE META O I ER

O I ER POOR META

LEGEND: ULTRA RAPID METABOLIZER = The enzymes for this group of drugs are too active and convert the medication too fast and remove it from the body. EXTENSIVE METABOLIZER = enzymes are functional and modify and break down certain drugs rapidly. INTERMEDIATE METABOLIZER = enzymes are inhibited or produced at a lower rate leading to a slower and break down of certain drugs. POOR METABOLIZER = no functional enzymes are being produced and so certain drugs are not broken down or metabolized correctly.

Page 18 of 38

Medical conse uence

Methylphenidate eg. Ritalin effectiveness 2 -30 VER E

ECTIVE

ESS E

ECTIVE â–²

Atome etine dosage ad ustments 13 33 NORMA

REA DO N

S O

.D. 1 - 0 â–²

NORMA DOSE

O ER DOSE 20-60 â–²

Drugs based on metho y amphetamines 33 NORMA

REA DO N

S O

.D. 1 - 0 â–²

NORMA DOSE

O ER DOSE 20-60 â–²

Results Summary Methylphenidate Ritalin : 'XH WR WKH SUHVHQW JHQHWLF YDULDQWV WKLV GUXJ ZLOO OLNHO\ EH OHVV HIIHFWLYH LQ WUHDWLQJ $'+' LQ WKH SDWLHQW > @ Atome etine: 7KH EUHDNGRZQ RI WKLV GUXJ LV VLJQLILFDQWO\ VORZHU WKDQ LQ WKH JHQHUDO SRSXODWLRQ DQG VR WKH GRVDJH VKRXOG EH VLJQLILFDQWO\ UHGXFHG WR DURXQG WR Drugs based on metho y amphetamines: 7KH EUHDNGRZQ RI GUXJV LQ WKLV FDWHJRU\ LV VLJQLILFDQWO\ VORZHU WKDQ LQ WKH JHQHUDO SRSXODWLRQ DQG VR WKH GRVDJH VKRXOG EH VLJQLILFDQWO\ UHGXFHG WR DURXQG WR

Page 19 of 38

R

CO E ET C

(IIHFW RQ UHOHYDQW GUXJV Drugs for epilepsy anticonvulsant effect

reakdo n

Adverse Reaction

recommended dose

alternative

likely higher

100

Normal

100

Not neccessary

mephenytoin

Normal

100

Normal

100

Not neccessary

phenobarbital

Normal

100

Normal

100

Not neccessary

phenytoin

Normal

100

Normal

100

Not neccessary

primidone

Normal

100

Normal

100

Not neccessary

retigabine

Normal

100

Normal

100

Not neccessary

reakdo n

Adverse Reaction

recommended dose

alternative

0

common

treatment Drugs for the of epilepsy dia epam

DA

Cough surpressants antitussive Drugs for suppressing cough de tromethorphan

DA

effect o None/

0

Advisable

Drugs for allergies antihistaminea treatment Drugs for the of allergic reactions

effect

reakdo n

Adverse Reaction

recommended dose

alternative

ole astemi

Normal

100

Normal

100

Not neccessary

chlorphenamine

Normal

100

Normal

100

Not neccessary

salmeterol

Normal

100

Normal

100

Not neccessary

terfenadine

likely higher

100

Normal

100

Not neccessary

theophylline

likely higher

100

Normal

100

Not neccessary

ileuton

Normal

100

Normal

100

Not neccessary

recommended dose

alternative

Appetite suppressants anorectic Hunger suppressants

effect

reakdo n

Adverse Reaction

de fenfluramine

Normal

0

common

0

Page 20 of 38

Advisable

Drugs for hyperactivity stimulants treatment Drugs for the of hyperactivity or narcolepsy

effect

reakdo n

Adverse Reaction

amphetamin

Normal

0

common

0

Advisable

amphetamine

Normal

0

common

0

Advisable

Normal

0

common

0

Advisable

effect

reakdo n

Adverse Reaction

recommended dose

alternative

likely higher

100

Normal

100

Not neccessary

cevimeline

Normal

100

Normal

100

Not neccessary

chlor o a one

Normal

100

Normal

100

Not neccessary

cisapride

Normal

100

Normal

100

Not neccessary

Normal

100

Normal

100

Not neccessary

Normal

100

Normal

100

Not neccessary

DA

Normal

0

common

0

Advisable

progesterone

Normal

100

Normal

100

Not neccessary

rilu ole

Normal

100

Normal

100

Not neccessary

sildenafil

Normal

100

Normal

100

Not neccessary

tadalafil

Normal

100

Normal

100

Not neccessary

Normal

0

common

0

Advisable

Normal

100

Normal

100

Not neccessary

DA

Normal

0

common

0

Advisable

se hormones

effect

reakdo n

Adverse Reaction

recommended dose

alternative

bicalutamide

Normal

100

Normal

100

Not neccessary

estradiol

Normal

100

Normal

100

Not neccessary

ethinylestradiol

Normal

100

Normal

100

Not neccessary

testosterone

Normal

100

Normal

100

Not neccessary

toremifene

Normal

100

Normal

100

Not neccessary

atomo etine

DA

recommended dose

alternative

Other Other drugs carisoprodol

DA

de lansopra ole

DA

finasteride modafinil

tetrabena ine

DA

ti anidine tolterodine

Hormones

Page 21 of 38

Proton pump inhibitors treatment Drugs for the of stomach ulcers

effect

reakdo n

Adverse Reaction

recommended dose

alternative

esomepra ole

DA

Normal

100

Normal

100

Not neccessary

lansopra ole

DA

likely higher

100

Normal

100

Not neccessary

omepra ole

DA

Normal

100

Normal

100

Not neccessary

Normal

100

Normal

100

Not neccessary

likely higher

100

Normal

100

Not neccessary

effect

reakdo n

Adverse Reaction

recommended dose

alternative

DA

Normal

10

common

0

Advisable

chlorproma ine

Normal

0

common

0

Advisable

cloba am

DA

Normal

100

Normal

100

Not neccessary

clo apine

DA

Normal

20

common

20

Advisable

escitalopram

Normal

100

Normal

100

Not neccessary

haloperidol

Normal

0

common

0

Advisable

Normal

0

common

Normal

0

common

Normal

0

common

0

Advisable

Normal

20

common

20

Advisable

uetiapine

Normal

100

Normal

100

Not neccessary

remo ipride

Normal

0

common

0

Advisable

pantopra ole

DA

rabepra ole

DA

Antipsychotics treatment Drugs for the of psychoses aripipra ole

iloperidone

DA

olan apine perphena ine pimo ide

DA DA

0 0

Advisable Advisable

risperidone

DA

Normal

0

common

0

Advisable

thiorida ine

DA

Normal

0

common

0

Advisable

iprasidone

Normal

100

Normal

100

Not neccessary

uclopenthi ol

Normal

0

common

0

Advisable

Page 22 of 38

Antidepressants treatment Drugs for the of clinical depression

effect

reakdo n

Adverse Reaction

recommended dose

alternative

agomelatine

Normal

100

Normal

100

Not neccessary

amitriptyline

likely higher

20

common

20

Advisable

buspirone

Normal

100

Normal

100

Not neccessary

citalopram

Normal

common

0

Advisable

clomipramine

Normal

0

common

0

Advisable

cycloben aprine

Normal

100

Normal

100

Not neccessary

desipramine

Normal

20

common

20

Advisable

dia epam

likely higher

100

Normal

100

Not neccessary

do epin

Normal

0

common

0

Advisable

dulo etine

Normal

0

common

0

Advisable

fluo etine

Normal

30

common

20

Advisable

fluvo amine

Normal

0

common

0

Advisable

imipramine

Normal

0

common

mianserin

Normal

0

common

0

Advisable

minaprine

Normal

0

common

0

Advisable

mirta apine

Normal

common

0

Advisable

moclobemide

Normal

0

common

0

Advisable

nefa odone

Normal

20

common

20

Advisable

norfluo etine

Normal

0

common

0

Advisable

nortriptyline

Normal

0

common

0

Advisable

paro etine

Normal

0

common

0

Advisable

protriptyline

Normal

0

common

0

Advisable

rebo etine

Normal

100

Normal

100

Not neccessary

sertraline

Normal

100

Normal

100

Not neccessary

tra odone

Normal

0

common

0

Advisable

Normal

0

common

0

Advisable

Normal

100

Normal

100

Not neccessary

likely higher

1

common

0

Advisable

trimipramine

DA

valproicacid venlafa ine

DA

0

Page 23 of 38

Advisable

Painkillers analgesics Painkillers

effect

reakdo n

Adverse Reaction

recommended dose

alternative

alfentanil

Normal

100

Normal

100

Not neccessary

buprenorphine

Normal

100

Normal

100

Not neccessary

likely higher

20

common

20

Advisable

enflurane

Normal

100

Normal

100

Not neccessary

fentanyl

Normal

100

Normal

100

Not neccessary

halothane

Normal

100

Normal

100

Not neccessary

hydrocodone

Normal

0

common

0

Advisable

isoflurane

Normal

100

Normal

100

Not neccessary

levacetylmethadol

likely higher

100

Normal

100

Not neccessary

lidocaine

Normal

100

Normal

100

Not neccessary

methadone

Normal

0

Normal

100

Not neccessary

metho yflurane

Normal

100

Normal

100

Not neccessary

o ycodone

Normal

0

common

0

Advisable

paracetamol

Normal

100

Normal

100

Not neccessary

phenacetin

Normal

100

Normal

100

Not neccessary

ropivacaine

Normal

100

Normal

100

Not neccessary

sevoflurane

Normal

100

Normal

100

Not neccessary

likely higher

40

common

0

Advisable

Normal

100

Normal

100

Not neccessary

codeine

tramadol

DA

DA

olmitriptan

Drugs for high blood pressure antihypertensive treatment Drugs for the of high blood pressure cardiac insufficiency and cardiac arrhythmia

effect

reakdo n

Adverse Reaction

recommended dose

alternative

amlodipine

Normal

100

Normal

100

Not neccessary

atacand

likely higher

100

Normal

100

Not neccessary

bosentan

Normal

100

Normal

100

Not neccessary

candesartan

Normal

100

Normal

100

Not neccessary

diltia em

Normal

100

Normal

100

Not neccessary

felodipine

Normal

100

Normal

100

Not neccessary

irbesartan

Normal

100

Normal

100

Not neccessary

lercanidipine

Normal

100

Normal

100

Not neccessary

losartan

likely higher

100

Normal

100

Not neccessary

nifedipine

Normal

100

Normal

100

Not neccessary

nisoldipine

Normal

100

Normal

100

Not neccessary

nitrendipine

Normal

100

Normal

100

Not neccessary

verapamil

Normal

100

Normal

100

Not neccessary

Page 24 of 38

Drugs for Infections antibiotics etc. Medication to combat infections

effect

reakdo n

Adverse Reaction

recommended dose

alternative

caspofungin

Normal

100

Normal

100

Not neccessary

clarithromycin

Normal

100

Normal

100

Not neccessary

erythromycin

Normal

100

Normal

100

Not neccessary

indinavir

Normal

100

Normal

100

Not neccessary

ole itracona

Normal

100

Normal

100

Not neccessary

ketocona ole

Normal

100

Normal

100

Not neccessary

nelfinavir

Normal

100

Normal

100

Not neccessary

nevirapine

Normal

100

Normal

100

Not neccessary

proguanil

likely higher

100

Normal

100

Not neccessary

likely higher

100

Normal

100

Not neccessary

Normal

100

Normal

100

Not neccessary

ritonavir

Normal

0

common

0

Advisable

sa uinavir

Normal

100

Normal

100

Not neccessary

telithromycin

Normal

100

Normal

100

Not neccessary

Normal

0

common

0

Advisable

Normal

100

Normal

100

Not neccessary

pyra inamide rifampin

terbinafine

DA DA

DA

voricona ole

DA

Drugs for traveling sickness antiemetic Drugs for easing the feeling of sickness

effect

reakdo n

Adverse Reaction

recommended dose

alternative

aprepitant

Normal

100

Normal

100

Not neccessary

dolasetron

Normal

0

common

0

Advisable

domperidone

Normal

100

Normal

100

Not neccessary

metoclopramide

Normal

0

common

0

Advisable

Recommendations for the dose are based on various studies that have been undertaken with many but not with all drugs on this list. As all drugs re uired similar ad ustments of dosage we can assume that this applies to other drugs on the list as well. owever this is not yet scientifically verified. Source: lockhart DA. Drug Interactions: ytochrome P Drug Interaction Table. Indiana University School of Medicine . http: medicine.iupui.edu clinpharm ddis table.asp .

Page 25 of 38

R

CO

ET C

7HFKQLFDO LQIRUPDWLRQ DERXW $'+' PHGLFDWLRQ This section summarizes the technical details of commonly prescribed AD D medication and is intended for e pert use. This information DOES NOT ET consider the information of the genetic test and should act as basis of how to modify the standard dose based on genetics

Indications: Methylphenidate Ritalin ➤ $WWHQWLRQ 'HILFLW +\SHUDFWLYLW\ 'LVRUGHU $'+' ➤ 1DUFROHSV\ ➤ 'HSUHVVLRQ LQ PHGLFDOO\ LOO HOGHUO\ SDWLHQWV ➤ (QKDQFHG SDLQ FRQWURO LQ SDWLHQWV RQ RSLDWHV

Contraindications ➤ 6HH 'UXJ LQWHUDFWLRQV EHORZ ➤ &RQJHQLWDO +HDUW 'HIHFW DVN UHODWHG 30+ )DPLO\ +LVWRU\ DQG VFUHHQ RQ $'+' H[DP

➤ &RQVLGHU DQ (.* EHIRUH SUHVFULELQJ ➤ 9HWWHU &LUFXODWLRQ ➤ 0RWRU 7LFV RU 7RXUHWWH V 6\QGURPH ➤ *ODXFRPD ➤ 6HL]XUH GLVRUGHU ➤ +\SHUWHQVLRQ ➤ 3UHJQDQF\

Pharmacokinetics: Methylphenidate ➤ ,PPHGLDWH 5HOHDVH 5LWDOLQ ,5 0HWK\OLQ ,5 ➤ 2QVHW RI DFWLRQ ZLWKLQ WR PLQXWHV RI GRVH ➤ 3HDNV DW KRXUV RQ DYHUDJH ➤ 'XUDWLRQ WR KRXUV

➤ ,PPHGLDWH 5HOHDVH )RFDOLQ 'H[PHWK\OSKHQLGDWH

➤ ' LVRPHU RI 5LWDOLQ O LVRPHU LV LQDFWLYH

➤ 3UHVFULEHG DW KDOI GRVH RI 5LWDOLQ ➤ 6DPH SKDUPDFRNLQHWLFV DV LPPHGLDWH UHOHDVH 0HWK\OSKHQLGDWH ➤ )HZHU +HDGDFKHV EXW PRUH 6WRPDFKH SDLQ WKDQ ZLWK 0HWK\OSKHQLGDWH

➤ /RQJ $FWLQJ 5LWDOLQ /$ ➤ 'XUDWLRQ KRXUV ➤ %LSKDVLF UHOHDVH ➤ ,PPHGLDWH UHOHDVH ➤ 0RGLILHG UHOHDVH EHDGV

Page 26 of 38

➤ 3UHIHUUHG RYHU 5LWDOLQ 65

➤ /RQJ $FWLQJ 5LWDOLQ 65 0HWDGDWH (5 0HWK\OLQ (5 ➤ 2QVHW RI DFWLRQ ZLWKLQ PLQXWHV RI GRVH ➤ 3HDNV DW KRXUV RQ DYHUDJH ➤ 'XUDWLRQ KRXUV JUDGXDO GHFUHDVH DIWHU KRXUV

➤ /HVV HIIHFWLYH WKDQ 5LWDOLQ ,5 ELG ➤ 2WKHU VXVWDLQHG UHOHDVH IRUPV DUH SUHIHUUHG

➤ 9HU\ /RQJ $FWLQJ &RQFHUWD ➤ 2QVHW RI DFWLRQ ZLWKLQ WR PLQXWHV RI GRVH ➤ 'XUDWLRQ KRXUV ➤ &RPSDUDEOH WR 5LWDOLQ ,5 WLG

➤ 9HU\ /RQJ $FWLQJ 0HWDGDWH &' ➤ )ODW FRQFHQWUDWLRQ FXUYH GHVSLWH ELSKDVLF UHOHDVH ➤ 'XUDWLRQ KRXUV ➤ %LSKDVLF SHDNV DW KRXUV DQG DJDLQ DW KRXUV ➤ ,PPHGLDWH UHOHDVH EHDGV ➤ ([WHQGHG UHOHDVH EHDGV

Page 27 of 38

Dosing: Children over age 6 years ➤ 0D[LPXP WRWDO GDLO\ GRVH PJ GD\ ➤ ,PPHGLDWH 5HOHDVH 0HWK\OSKHQLGDWH ➤ 8VXDO 5DQJH PJ NJ GD\ ➤ 6WDUW WR PJ SHU GRVH WZLFH GDLO\ ➤ ,QLWLDO 6FKHGXOH ODVWV KRXUV GRVH XS WR WLPHV GDLO\

➤ 0RUQLQJ WR PJ 32 PLQXWHV EHIRUH EUHDNIDVW ➤ 1RRQ WR PJ 32 PLQXWHV EHIRUH OXQFK ➤ $IWHUQRRQ WR PJ 32 DW SP ➤ 7LWUDWH GRVH XS ZHHNO\ ➤ ,QFUHDVH GRVH E\ PJ NJ GRVH RU PJ GD\

➤ 0D[LPXP GRVH PJ NJ GD\ RU PJ GD\ VRPH VRXUFHV VXJJHVW PD[LPXP XS WR

➤ ,PPHGLDWH 5HOHDVH )RFDOLQ 'H[PHWK\OSKHQLGDWH

➤ 6WDUW PJ RUDOO\ WZLFH GDLO\ ➤ 8VXDO 'RVH PJ RUDOO\ WZLFH GDLO\ ➤ 0D[LPXP 'RVH PJ RUDOO\ GDLO\

➤ 6XVWDLQHG 5HOHDVH ➤ &RQFHUWD WR PJ RUDOO\ GDLO\ ➤ 6WDUW PJ T$0 ➤ 0D\ LQFUHDVH ZHHNO\ E\ PJ GD\ ➤ &RQYHUVLRQV ➤ 5LWDOLQ PJ RU PJ 65 &RQFHUWD PJ ➤ 5LWDOLQ PJ RU PJ 65 &RQFHUWD PJ ➤ 5LWDOLQ PJ RU PJ 65 &RQFHUWD PJ ➤ 0D[LPXP PJ GD\ ➤ 5LWDOLQ /$ RU 0HWDGDWH &' ➤ 6WDUW PJ RUDOO\ GDLO\ ➤ 0D\ LQFUHDVH ZHHNO\ E\ PJ GD\ ➤ 8VXDO GRVH PJ RUDOO\ RQFH GDLO\ ➤ 0D[LPXP PJ GD\ ➤ 5LWDOLQ 65 2WKHU ORQJ DFWLQJ DJHQWV DUH SUHIHUUHG

➤ 'RVH WR PJ NJ XS WR PJ RUDOO\ GDLO\ ➤ 'RVH LV GLUHFWO\ FRQYHUWHG IURP 5HJXODU 5LWDOLQ ➤ &RQYHUVLRQ WR 5LWDOLQ 65 0HWDGDWH (5 0HWK\OLQ (5

➤ $GPLQLVWHU FXPXODWLYH KRXU UHJXODU GRVH ➤ ([DPSOH &RQYHUVLRQ ➤ &KLOG WDNHV 5LWDOLQ PJ PJ DQG PJ ➤ 5LWDOLQ 65 GRVLQJ ZLOO EH PJ T$0 ➤ ([DPSOH 6FKHGXOH ➤ 0RUQLQJ PJ RUDOO\ ➤ (DUO\ DIWHUQRRQ PJ RUDOO\ ➤ 'D\WUDQD 0HWK\OSKHQLGDWH SDWFK

➤ 6WDUW PJ SDWFK ZRUQ KRXUV GDLO\ ➤ 0D[ PJ SDWFK ZRUQ KRXUV GDLO\ ➤ 6NLQ LUULWDWLRQ RU UDVK PD\ RFFXU

Page 28 of 38

Dosing: Adults ith ADHD or Narcolepsy ➤ 0D[LPXP WRWDO GDLO\ GRVH PJ ➤ 5HJXODU 5HOHDVH WR PJ 32 ELG WR WLG DW PHDOV ➤ 6XVWDLQHG 5HOHDVH PJ 32 XS WR T KRXUV

Dosing: Elderly ith comorbid Depression ➤ 0D[LPXP WRWDO GDLO\ GRVH PJ ➤ 5HJXODU 5HOHDVH WR PJ ELG WR WLG

Drug Interactions ➤ $YRLG FRQFXUUHQW 'HFRQJHVWDQW XVH ➤ $YRLG ZLWKLQ GD\V RI 0$2 LQKLELWRU

Monitoring ➤ +HLJKW ➤ :HLJKW ➤ %ORRG 3UHVVXUH ➤ 3XOVH

Adverse Effects ➤ 5HERXQG $'+' EHKDYLRU ZKHQ PHGLFDWLRQ OHYHO ZDQHV ➤ (PRWLRQDO ODELOLW\ LUULWDELOLW\ RU WHDUIXOQHVV ➤ 6RFLDO ZLWKGUDZDO ➤ )ODW DIIHFW ➤ ,QVRPQLD ➤ 3RRU DSSHWLWH ➤ 6WRPDFK SDLQ ➤ 8QLQWHQWLRQDO :HLJKW /RVV ➤ 5HGXFHG JURZWK YHORFLW\ ➤ +HDGDFKH ➤ 3V\FKRVLV DW H[FHVVLYH GRVHV

References ➤ /H[LFRPS 'UXJ 'DWDEDVH ➤ 3HGLDWULFV ➤ $QGHVPDQ 3HGLDWU &OLQ 1RUWK $P ➤ %HQQHWW 3HGLDWU &OLQ 1RUWK $P ➤ &KDOOPDQ 0D\R &OLQ 3URF

Drug Interactions ➤ Carbama epine &DUEDPD]HSLQH PD\ GHFUHDVH WKH HIIHFW RI PHWK\OSKHQGLDWH

➤ Cyclosporine 0HWK\OSKHQLGDWH LQFUHDVHV WKH HIIHFW DQG WR[LFLW\ RI F\FORVSRULQH

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➤ Guanethidine 0HWK\OSKHQLGDWH PD\ GHFUHDVH WKH HIIHFW RI JXDQHWKLGLQH

➤ Isocarbo a id 3RVVLEOH K\SHUWHQVLYH FULVLV ZLWK WKLV FRPELQDWLRQ

➤ Phenel ine 3RVVLEOH K\SHUWHQVLYH FULVLV ZLWK WKLV FRPELQDWLRQ

➤ Trandolapril 0HWK\OSKHQLGDWH PD\ DQWDJRQL]H WKH DQWLK\SHUWHQVLYH HIIHFW RI 7UDQGRODSULO 0RQLWRU IRU FKDQJHV LQ EORRG SUHVVXUH LI 0HWK\OSKHQLGDWH LV LQLWLDWHG GLVFRQWLQXHG RU GRVH FKDQJHG

➤ Tranylcypromine 7KH 0$2 LQKLELWRU 7UDQ\OF\SURPLQH PD\ LQFUHDVH WKH YDVRSUHVVRU HIIHFW RI 0HWK\OSKHQLGDWH &RQFRPLWDQW WKHUDS\ LV FRQWUDLQGLFDWHG

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Analysis for ifestlye-purposes

Analysis of medical genetic samples

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Medical interpretation of genetic analyses

Scientific release of analysis results

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TEC

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Method of analysis

2ORI $VNOXQGVJDWD 9lVWUD )U|OXQGD 6:('(1

$XWRPDWHG '1$ H[WUDFWLRQ +50 DQDO\VLV DV QHHGHG PDVV VSHFWURPHWU\ DQG 7DT0$1 UHDO WLPH 3&5

Order number '(02B'1$0(',&

Detection rate a

Date of birth

Sample type &KHHN VZDE VDOLYD VDPSOH

Responsible company '1$ 0(',& 6&$1',1$9,$ $% 2/2) $6./81'6 *$7$ 6 9b675$ )5g/81'$ 6:('(1

Analysis times 6DPSOH UHFHLYHG $QDO\VLV VWDUWHG $QDO\VLV FRPSOHWHG 5HSRUW JHQHUDWHG

Analy ing laboratory 1RYRJHQLD *PE+ 6DDODFKVWUDVVH 6DO]EXUJ $8675,$

aboratory director 'U 'DQLHO :DOOHUVWRUIHU % 6F

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RE ERE CE

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