Skip to main content
Premium Trial:

Request an Annual Quote

VA's Million Veteran Program Hoping to Translate Data Insights into Better Care

genetic mutation - Getty Images.jpg

NEW YORK – Having reached its namesake milestone of enrolling 1 million participants over the past nearly 13 years, the US Department of Veterans Affairs' Million Veteran Program will focus over the coming decade on applying the collected data to improving healthcare for all. 

Since 2011, the MVP has amassed medical, genetic, and lifestyle data from veterans, including information on their military experiences and toxic exposures. That has opened doors for researchers to probe how genetic and environmental factors influence numerous health conditions. In fact, over the years, researchers involved in the MVP have published more than 350 research papers based on data from the project, said Sumitra Muralidhar, the director of the program.

Now, after having reached its enrollment goal in late 2023, Muralidhar said the program is turning a corner and putting an eye on translating its research findings into clinical care — including supporting development of potential new therapeutics. "The whole goal of building this program was not only to advance science but also to improve healthcare," she said. "We're really going to focus in the next decade on bringing research discoveries into the clinic."

The Veterans Health Administration provides an ideal study population in many ways, Muralidhar added, since veterans continue to receive care at the VA system throughout their lives, enabling the development of a longitudinal dataset. "We have a stable patient population," she said. "Once veterans come to the VA to get healthcare, they pretty much stay with the system."

Despite the program's name, Muralidhar said the MVP will "absolutely continue" to enroll past the 1 million participant mark. Researchers will focus on recruiting participants from underrepresented groups to ensure findings are generalizable across race, ethnicity, and other demographic factors.

That means that since only 9 percent of US veterans are women but 50 percent of the country's population, researchers must try to recruit more women into the MVP, which has 100,000 women participants, or 10 percent of the enrolled population. 

For certain racial and ethnic groups, the proportion of MVP participants exceeds their representation in the overall US population. For example, about 18 percent of enrollees have African ancestry, surpassing the proportion of Black individuals in the US, which is 14.2 percent, according to the most recent census in 2020. 

Similarly, Native Hawaiians and Pacific Islanders make up 1 percent of MVP enrollees, compared to 0.5 percent of the US population. 

The diversity of data from these participants has already helped researchers uncover novel healthcare insights. In one study, the results of which were published in the Journal of the American Society of Nephrology in November, investigators analyzed genetic and health data from participants with African ancestry and identified a genetic marker that seems to protect some Black patients against kidney disease and reduce their risk of developing the condition even when they have other high-risk biomarkers.

There are striking racial inequities in kidney disease outcomes, with Black patients having a fourfold higher risk of progressing to end-stage disease, pointed out Adriana Hung, lead author of the study and a nephrologist and epidemiologist at Vanderbilt University Medical Center. "We have been pulling our hairs [out], thinking: 'What can be the cause of this inequality?'" she said.

Genetics is certainly a component. For years, researchers have known that carrying two copies of a certain high-risk variant in the APOL1 gene can cause damage to kidney cells, and patients with those variants have an increased risk of developing kidney disease and rapid disease progression. The variant is common among Black patients, with roughly 45 percent of patients carrying at least one high-risk variant and nearly 13 percent carrying two, Hung and colleagues wrote in a JAMA Internal Medicine paper in 2022. While having one copy of the variant is thought to protect against certain infections, the negative implications for kidney health still disproportionately affect individuals of African ancestry in the US.

The protective variant identified in Hung's research, APOL1 p.N264K, specifically blocks the APOL1 proteins from damaging kidney cells and was found to reduce the risk of developing chronic kidney disease or end-stage kidney disease in carriers. In fact, among patients with the high-risk APOL1 variants, also carrying the p.N264K variant reduced their risk to levels similar to those who don't have the high-risk variants.

But, while the harmful variant is fairly common, the protective one is rare, and this is where the MVP data came into play. The project provided researchers with a robust dataset to identify not only individuals with the protective variant but also to allow them to study how that mutation interacts with the previously known harmful variants. "What made it possible was the diversity and the large sample size that the Million Veteran Program had achieved," Hung said.

Hung and colleagues conducted their analysis on data from the MVP and validated it with data from the US National Institutes of Health's All of Us Research Program and the biobank at Vanderbilt University Medical Center.

Now, Hung sees an opportunity for APOL1 inhibitors that mimic the role of the APOL1 p.N264K variant by blocking the function of APOL1 proteins as potential treatments for kidney disease. There are currently biopharmaceutical companies developing such therapies, and Hung said she's working to have some VA centers serve as clinical sites for one Phase III trial.

The MVP study provides "very strong support that these medications should [have] beneficial effects to prevent dialysis and kidney disease in individuals of African ancestry," she said.

The VA did not respond to a request for comment on which APOL1 inhibitor trial may be initiated at its centers. However, Maze Therapeutics is testing MZE829, a small molecule APOL1 inhibitor, in a Phase I trial and plans to publish results from it in the second half of 2024. Vertex Pharmaceuticals is also gearing up to begin the Phase III portion of an ongoing Phase II/III trial of its small molecule APOL1 inhibitor inaxaplin.

That's the kind of clinical-stage research Muralidhar is hoping the MVP data will inspire and, eventually, lead to changes in patient care. As another example, she highlighted that researchers have used the MVP data to develop a polygenic risk score that can identify those at risk of developing prostate cancer. The VA recently launched a clinical trial to compare the risk score's prognostic capabilities alongside standard screening.

The MVP this year will also increase the types of molecular data it is collecting and analyzing to include whole-genome sequencing, metabolomics, and proteomics data on 100,000 participants. That can bolster investigators' ability to not only uncover more genetic associations but also garner deeper insights on the role of gene expression, Muralidhar said.

While every participant who enrolls into the MVP provides a blood sample for genotyping, just about 150,000 of the samples have undergone whole-genome sequencing so far.

Muralidhar said she's particularly interested in how the MVP can leverage its data to better understand how genetic variation may influence how veterans respond to particular toxic exposures during military service as well as study how certain exposures interact with genetics. The MVP has set up a task force to explore these research questions. It's an important area of study in light of the Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics Act of 2022, better known as the PACT Act, which expanded healthcare and benefits for veterans with cancer and other diseases caused by exposure to toxic substances in military duty.

Expanding the "data universe" will be key to the MVP's vision of being able to answer these questions "even more comprehensively," Muralidhar said.