A Database of a Million Veterans

The goal is simple but ambitious: collect samples and medical data from a million American veterans to create an enormous database of medical information. For Philip Tsao, PhD, research professor of cardiovascular medicine, and Lawrence Leung, MD, Maureen Lyles D’Ambrogio Professor of Medicine and senior associate dean for Veteran Affairs, the Million Veterans Program, or MVP, is a way to enhance both veterans’ health and the medical field in general.

Tsao and Leung have been collaborators for years, and when Leung started work as chief of staff at the Palo Alto VA, he invited Tsao to join him. Leung believed that the VA — a nationally integrated hospital system with records that went back decades, and in fact the first adopter of what is now the EHR or electronic health record—was an ideal place for genomics research.

So seven years ago Tsao moved his lab to the VA, and they began their work. Both doctors thought the Palo Alto VA in particular was an excellent site for genomics research, with roughly 1,000,000 outpatient encounters per year and a close relationship with Stanford, where they’d be able to, as Tsao says, “leverage the local talent” in various departments, including medicine, genetics, and statistics. Tsao explains that the VA would provide “an opportunity to really quickly collect a large cohort.”

The Beginnings of MVP

Leung and Tsao’s interest in genomics research led them to Washington, DC, where they hoped to pitch their project plans to national VA leaders. Ironically, that was when they found out about the MVP program, an effort much like theirs that was already in motion. That was 2011, and now over 50 VA sites across the country are recruiting individuals for MVP. The program has passed 700,000 participants, “well on the way to a million,” Tsao says. Now they’re thinking of surpassing a million.

MVP participants donate at least four sources of data: a blood sample, access to their electronic health record, a baseline lifestyle survey with demographic information, and a more extensive lifestyle survey with detailed dietary information as well as other medical statistics. All participants can opt out of any part of the voluntary program, but many do everything, including the longer lifestyle survey.

They’re also asked to consent to be re-contacted once their data has been processed. For Tsao this is a crucial part of the project both for the veterans and the larger medical world: Their data can be revisited, their health resampled to “see how their biological signals are changing over time.” And if researchers discover a correlation between, for example, genomic material and a particular disease, they can go back to individuals and study them in more detail, in what Tsao describes as “types of fine mapping studies” that will be crucial as the program goes forward.

Veterans proved to be ideal genomic study subjects for another reason: their patriotism. “They’re very much interested in continuing to serve their country,” Tsao says, adding that he’s heard dozens of participants say that participating in MVP is “one way they can contribute, not only to their brothers in arms but also to their country. The research effort may not help them individually but it will help not only their brothers but also generations to come. Veterans are very interested in research that will pay forward.”

Translating Data into Results

So far, so good. But the next step is both daunting and slightly ambiguous: What will they do with all the information they’ve collected? Seven years in, the data is being organized, and qualified researchers are beginning to access it. As Tsao states, “Some of our first papers are just coming out, and we’re very excited about not only what has been done up to this point, but the potential of the study itself.” For example, the team at Stanford/Palo Alto VA has recently published a study in Nature Genetics that greatly expands the number of genetic factors that contribute to lipid levels. (High levels of these blood fats are a major risk factor for heart disease.)

The possibilities raised by this type of data are exciting. “We know that certain risk factors such as blood pressure and your cholesterol level are important for heart attacks, and we now can go back decades and get people’s cholesterol levels over time. We can look at their maximum cholesterol level, we can look at the trajectory, and we can look at what the interaction with different drugs may have been.”

The Palo Alto VA has also launched its own center: the VA Palo Alto Epidemiology Research and Information Center, or ERIC, to facilitate the analysis of MVP-gathered data. The center will take advantage of the proximity to Stanford and involve contributions from many Stanford-based programs in harvesting MVP’s data for research. Collaborators include Tim Assimes, MD, PhD, associate professor of cardiology and epidemiology; Michael Snyder, MD, Stanford W. Ascherman Professor and chair of the department of genetics; Wing Wong, PhD, Stephen R. Pierce Family Goldman Sachs Professor in Science and Human Health and professor of biomedical data science; and Hua Tang, PhD, professor of genetics and statistics.

“There’s a diverse and deep amount of talent at Stanford,” Tsao says. This type of collaboration leads to novel methods to approach biology. Tsao, Leung, Snyder, and colleagues recently published a paper describing a new technique that harnesses the power of machine learning applied to genetic data and health records.

Tsao and Leung are currently co-directors of the Palo Alto MVP program, as well as co-directors of ERIC with Assimes. Tsao is one of the three principal investigators for the nationwide MVP program, and he’s the principal investigator of one of the first approved studies to examine the MVP data: a study on cardiometabolic disease with Assimes and Jennifer Lee, MD, PhD, associate professor of endocrinology and epidemiology. Lee and Assimes are also involved in a study to incorporate some of the work of Nigam Shah, MBBS, PhD, associate professor of biomedical informatics, into the VA electronic health record to improve the phenotyping of individuals, which they will then apply to their genomics work. 

The Future of MVP

The far-reaching goals of MVP can overwhelm, Tsao says. “One of the fears would be that we make a lot of discoveries and then we inundate both patient and provider to a point where it becomes more harm than good,” he explains. “Beyond the science there’s a whole host of work that needs to be done to integrate this into health care.”

But he’s optimistic about its overarching hopes. “The ultimate goal would be to discover diagnostics, prognostics, and theranostics that could be eventually brought into the clinic. And of course understanding the basic underpinnings of disease and how we can apply those to identify individuals who are at risk, and then help in the management of both disease and health.”

Both Leung and Tsao clearly believe in the enormous potential of this study. “MVP is the crown jewel of VA research,” Leung says. “Palo Alto VA, in close partnership with the Stanford School of Medicine, will continue to play a leading role in the translation of this program in defining precision medicine.”