Years before the international Human Genome Project determined the sequence of chemical base pairs that make up human DNA, researchers at the Department of Veterans Affairs (VA) were pioneers in this new line of inquiry, uncovering links between specific genes – the segments of DNA that form the molecular units of heredity – and particular diseases or disorders. Beginning in the mid-1990s, investigators at the VA’s Puget Sound Health Care System made a series of discoveries linking genetic mutations to Werner’s syndrome (a rare hereditary disease that causes premature aging and death), schizophrenia, and a rare form of dementia. This 1998 discovery offered a potential target for the treatment of Alzheimer’s disease.

Genetic studies are generally of two types: candidate gene studies, in which researchers focus on associations between pre-specified genetic variations and disease states, or genome-wide association studies (GWAS), which scan the entire genomes of a large sample of people for common genetic variations, and, with the help of super-fast computers, discover which genes turn up in one group (i.e., people with diabetes) and not another.

When the 13-year effort to map the entirety of the human organism’s hereditary material – the genome – was finalized in 2003, it sparked an explosion in genomics research, and the VA, with several successful investigations already completed and more underway, assumed a leading role in this new era. In 2006, to advance knowledge of how genes affect health and to examine the potential for emerging genomic technologies to personalize medicine for veterans, the agency formally established its Genomic Medicine Program.

The first steps in launching the program included the establishment of a distinguished 13-member Genomic Medicine Program Advisory Committee (GMPAC) to lay the groundwork and chart a course for investigation. Meanwhile, the Veterans Health Administration (VHA) broadened its network of laboratories conducting genomics research; at the Washington, D.C. VA Medical Center, for example, investigators began looking into genetic changes in cancers that might predict responses to chemotherapy and guide patient care.

Genomic research promises to change the field of medicine completely, offering evidence-based and personalized approaches to prevention, diagnosis, and treatment. A significant portion of genomics research today is devoted to the field of pharmacogenomics, or studies of how individual genes determine a person’s reaction to certain drugs or immunotherapies.

Genetic studies are generally of two types: candidate gene studies, in which researchers focus on associations between pre-specified genetic variations and disease states, or genome-wide association studies (GWAS), which scan the entire genomes of a large sample of people for common genetic variations, and, with the help of super-fast computers, discover which genes turn up in one group (i.e., people with diabetes) and not another.

Sumitra Muralidhar, PhD, director for the Million Veteran Program (MVP), in the VHA’s Office of Research and Development, pointed out that several things need to be in place before a useful GWAS can be implemented, including a large sample of genetic material, the infrastructure necessary to store and examine it, and powerful informatics and computational tools to compare hundreds of thousands to millions of variants.

The VHA is, in many respects, the ideal venue for genomics research. It’s the nation’s largest integrated health care delivery system, providing care to about 8.8 million veteran patients; it uses one of the world’s most sophisticated electronic medical record systems; many of its investigators are also esteemed faculty members at the nation’s finest research universities; and its professionals are committed to personalizing medicine to the greatest extent possible. The sheer number of patient volunteers has allowed the VA to launch some of the world’s largest genomics studies. In 2009, a VA-funded research team, including Muralidhar, began investigating the genetic basis of schizophrenia and bipolar disorder, which together affect some 170,000 VA patients. Researchers in this GWAS are scanning DNA from upward of 29,000 veterans (~9,000 with either illness and at least 20,000 controls without either illness) in search of gene variants found in those with mental illness. VA’s research in the genetics of schizophrenia has led scientists to discover genes that weren’t on anyone’s radar a few years ago.