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The Million Veteran Program: Building VA’s Mega-Database for Genomic Medicine

November 19th, 2012

This year marks the fiftieth anniversary of Watson and Crick (and Wilkins) being named Nobel Prize recipients for discovering DNA, the genetic code. In the half century since, there has been an exponential growth of knowledge and accomplishment based on their findings. More recently, a confluence of scientific and technical advances have made possible vast progress in our understanding of human disease, its diagnosis, and the most effective treatment(s). Among these advances are genetic testing, high performance computing platforms, and the electronic health record (EHR), which together offer the possibility of clinically rich databases that link genetic information to treatment outcomes.

These and other advances have made it clear that the genetic predispositions to adult diseases are in many cases extremely complex. In its early phases, human genetics focused on single genes for single diseases that generally occurred in childhood; e.g., Tay-Sachs disease. The genomics of adult diseases—such as coronary heart disease—are associated with complexity resulting from multigene interactions and strong environmental influences (e.g., lifestyle and exposures), that may in some cases result in organ-specific “epigenetic” changes that modify DNA.

A prominent example of how these various factors come together can be seen by looking at diabetes. Having a gene associated with diabetes may modestly increase one’s chances of developing this condition from—let us say—6 to 12 percent. But whether diabetes actually results is influenced by additional factors, such as the sequences of other genes, environmental influences (such as diet and exercise), and age.

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