V E TE R AN S AFFAI R S & M I LITARY M E D I CI N E O UTLO O K
VA Research
PUTTING DATA TO WORK FOR VETERANS By Craig Collins
n IN THE ERA OF BIG DATA, there aren’t many public entities with bigger data than the Veterans Health Administration (VHA). The nation’s largest integrated health care network, serving about 9 million veterans, was an early adopter of electronic medical records, beginning in the 1970s. This digital platform has evolved over the years and now constitutes an electronic health record that contains inpatient and outpatient diagnoses and procedures, lab results, prescriptions, and other veteran medical data. In total, VHA has compiled more than 78 billion records from all of its VA medical centers. At the same time, the VHA’s groundbreaking efforts to understand how genes affect health and illness continue to grow. The most prominent of these efforts, the Million Veteran Program (MVP), was launched in 2011 to learn how genes, lifestyle, and military exposures interact to affect health and illness. To date, about 850,000 veteran volunteers have donated genetic samples – vials of blood – to aid in studies that look for associations between genes and medical record data, as well as self-reported survey data on lifestyle and military exposures. The investigations enabled by the collection of genetic material are generally of two types. The first, genotypic or “candidate gene” studies, focus on associations between pre-specified genetic variations and disease states. VHA investigators were pioneers in these kinds of studies; beginning in the mid-1990s, investigators at the Puget Sound Health Care System made a series of discoveries linking genetic mutations to Werner’s syndrome (a hereditary disease that causes premature aging and death), schizophrenia, and dementia. When the international Human Genome Project showed how to map the entire sequence of chemical base pairs that make up human DNA, it opened the door to a new kind of investigation: the genome-wide association study, or GWAS, in which entire genomes from a large cohort of people are scanned for common genetic variations. With the help of powerful supercomputers, investigators discovered which genes appear in one group – such as people with breast cancer – and not another.
52
A useful GWAS requires several elements: a large sample of genetic material, the infrastructure necessary to store and examine it, and powerful computational tools for comparing hundreds of thousands, maybe even millions, of variants. Samples from MVP participants are collected and stored in a massive freezer at the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) within the Boston VA facility. The 850,000 DNA samples, taken from veterans enrolled in MVP, are sorted, stored, and retrieved by a sophisticated robotic system. Great pains have been taken to guarantee the security of this data and the anonymity of donors. Names are removed from samples immediately; each participant becomes an anonymous blood vial, and data collected from other potentially identifying information, such as surveys, are assigned codes. According to Sumitra Muralidhar, PhD, who directs the Million Veteran Program, the point of building such a massive trove of genetic samples is to enable comparison studies on a scale that will reveal hidden secrets. “We’ll have sufficient numbers of people with a disease and without a disease,” she said, “and we’ll compare their genetics, so we can then identify what genetic risk factors may be associated with a certain disease.” Most MVP studies to date have compared genotypes – differences in the DNA sequences stored in the MAVERIC – with phenotypes, which Muralidhar defines as simply any observable characteristic or trait. “A phenotype could be as simple as the color of your hair or the color of your eye,” she said. “It could be a disease like diabetes. PTSD is a phenotype.” Post-traumatic stress disorder is a complex phenotype with many variations, Muralidhar said, as is a multi-variable condition like cardiovascular disease. “Lipid level, blood pressure – all of these are what we call phenotypes: biochemical, biomedical characteristics that result from the genes we have.” In less than a decade of existence, the power of the VHA’s considerable data stockpile has been made evident in landmark studies comparing genetic information to the phenotypes described in electronic health records and other data sources.
www.defensemedianetwork.com
