VA launched the Million Veteran Program (MVP) in 2011, with the goal of enabling genomic discoveries that can translate into improvements in health care for Veterans and the nation at large. With nearly 500,000 Veterans enrolled to date, the program is already one of the world’s largest databases of health and genomic information. The database is expected to serve as a national resource for an unprecedented scope of discovery, including in precision medicine.
Participation in MVP is available to Veterans enrolled in the VA Healthcare System. The coded data are being made available for approved research projects to a broad community of authorized researchers from VA and other federal and academic institutions. Stringent safeguards are in place to protect Veterans’ privacy.
A large portion of the DNA samples collected through MVP have already been analyzed through a process called single nucleotide polymorphism, or SNP, genotyping. This process looks for specific variants that may be linked to certain health conditions. Smaller subsets of the DNA have been analyzed through whole genome or whole exome sequencing. These methods “read” either the entire genome—all the genes found in a person’s DNA—or at least that portion known to code for proteins that carry out various functions in the body. Each of these methods has unique benefits and limitations. All three can provide insight into the role of genes in health and disease.
The first research projects, that have been coined alpha and beta studies, are underway which will help optimize the process by which authorized researchers can securely access and analyze MVP data. These studies will lay the foundation for expanded access for researchers at partner institutions, including the Department of Defense, the National Institutes of Health, and leading universities. Below are brief descriptions of the current alpha and beta studies .Within the next few years, these and other studies using MVP data will likely lead to new ways to prevent and treat disease.
Gulf War Illness risk factors – Dr. Drew Helmer at the VA New Jersey Health Care System and Dr. Dawn Provenzale at the VA Cooperative Studies Epidemiology Center in Durham are examining the genes that influence the development of Gulf War Illness (GWI). Using MVP data, their team will compare “case” patients with healthy “controls” and look at the relationships among genetic variations, self-reported Gulf War environmental exposures, and susceptibility to GWI.
Posttraumatic stress disorder risk factors – Dr. Murray Stein at the VA San Diego Healthcare System and Dr. Joel Gelernter of the VA Connecticut Healthcare System are leading an effort probing the genes that influence the development of PTSD in combat-exposed Veterans. Using MVP data, their team will conduct one of the largest genetic studies of PTSD to date and help improve understanding of PTSD neurobiology.
Functional disability in schizophrenia and bipolar disorder – Dr. Philip Harvey at the Miami VA Healthcare System and Dr. Larry Siever at the James J. Peters VA Medical Center in the Bronx, N.Y., are leading a multicenter observational study to examine the genetic factors that affect the development of schizophrenia or bipolar disorder and the functional disability and cognitive impairment that accompany these conditions. They will compare “case” patients with either diagnosis who were recruited for the study with healthy “controls” who are part of the MVP database.
Genetic vulnerability for sustained multi-substance use– Dr. Daniel Federman and Dr. Amy Justice at the VA Connecticut Healthcare System and Dr. Henry Kranzler at the Philadelphia VA Medical Center are looking at genetic risk factors for chronic use of alcohol, tobacco, and opioids—and the dangerous use of all three together.
Genetics of cardiometabolic diseases in the VA population – Dr. Philip Tsao at the VA Palo Alto Health Care System and Dr. Kyong-Mi Chang at the Philadelphia VA Medical Center are leading a study to explore the role of genetics in obesity, diabetes, and abnormal lipid levels (namely, cholesterol and triglycerides), as drivers of heart disease. This project is expected to lead to a better understanding of the underlying causes of cardiometabolic disease and to new therapies that are safe, effective, and personalized.
Pharmacogenomics of kidney disease – Dr. Adriana Hung at the VA Tennessee Valley Healthcare System is leading a study focusing on how genes affect the risk and progression of kidney disease. One goal is to examine how patients with diabetes—who often develop kidney problems—respond differently to the drug metformin, the standard first-line treatment for diabetes, based on their genetic profile. The project will also look at the genetics of hypertension, a major risk factor for kidney disease.
Cardiovascular disease risk factors and genetics – Dr. Peter Wilson at the Atlanta VA Medical Center and Dr. Kelly Cho at the Boston VA Healthcare System are leading an effort probing the genes that influence how obesity and lipid levels affect heart risk. Using MVP data, this study will also look at whether these genetic factors differ among African Americans and Hispanics.
Genetic risk for macular degeneration – Drs. Eric Konicki and Neal Peachey at the Louis Stokes Cleveland VA Medical Center and Dr. Steven Fliesler at the VA Western New York Healthcare System in Buffalo are leading a project to determine whether age-related macular degeneration (AMD) susceptibility genes identified to date in Caucasian Americans are shared in African Americans. This question is important because recent advances in AMD genetics are being used to develop new therapeutics to slow or halt vision loss in the more prevalent forms of the condition.
About the author: The Veterans Health Administration contributed this article.