The donation of DNA samples from veterans is helping researchers identify early prevention and treatment for a variety of diseases.
The Department of Veterans Affairs (VA) launched its Million Veterans Program (MVP) in 2011 – one of the world’s largest genetic research programs to bring personalized medicine to VA care – with a goal to enroll one million veterans.
There are now more than 1.1 million veterans enrolled in MVP that represent 90% male and 10% female, and over 25% from minority racial backgrounds.
“Each person that has joined the program is adding a new dimension. They're bringing their experience to the program, and the more enrollees we have, the more representation, the more we can learn and take it back to the clinic,” said Dr. Sumitra Muralidhar, director of the MVP and Acting Deputy Chief Research and Development Officer.
MVP is the largest research program in the VA that studies how genetics, lifestyle, military experiences and exposures influence a veteran’s health and wellness through donated DNA samples. It’s open to all veterans who served in the U.S. military with an honorable discharge, and enrollment in the VA health system is not a requirement to participate.
Veterans can easily enroll online and schedule an appointment to provide a blood sample at a VA medical center. Or, a blood sample kit can be requested and mailed home to the veteran.
“I think the most important thing is spreading the word about the program so veterans can learn how it benefits veterans at large. And what we learn is not going to just help veterans. It will help all people,” Muralidhar said.
The data collected is used by researchers to better health conditions that matter to veterans. This includes predicting the risk of breast cancer, prostate cancer, diabetes, Alzheimer’s disease, endometriosis, osteoarthritis, impacts of military exposures and studying ways to better identify and treat mental illnesses like post-traumatic stress disorder.
The American Legion recently spoke with Muralidhar about current research MVP is conducting and the advancements it will provide to veterans and their overall healthcare.
What has the diverse population of veterans represented in the MVP allowed for research advancements in veteran healthcare?
What this has allowed us to do is really study genetics and other contributing risk factors across populations. I will add that it's not just where they're from or what age or ancestry, but also medical conditions, what kind of health conditions are represented in the cohort. Almost every condition that's seen in veterans is represented. As you know, mental health is one of the health conditions that we treat a lot in the VA, and so we decided to enrich that population in the cohort, and we developed a specific survey for mental illness. That's now been launched so we can get more veterans with mental illness represented in the cohort. And similarly, with military exposures, we've never had good information on the types of exposures veterans have had. So we launched a military toxic exposure survey last year. And over 250,000 veterans have responded. So we've expanded that cohort with all this new information on exposures that can now be studied through research. (When veterans enroll in the MPV, they can complete the mental health and toxic exposure surveys.)
What research is MVP studying and what discoveries for veteran treatment can this lead to?
We have over 120 research projects, and we are looking across various conditions, mental health, PTSD, depression, substance use disorders, heart disease, kidney disease, cancer, across the board, Gulf War illness, you name it and there's a study looking at it. We have over 550 peer-reviewed publications that have come out of all the studies that are using MVP data for research. One example is looking at Agent Orange and genetics risk. And this is for cancer, lymphatic cancers, lymphoma, leukemia. It's already known that there is a genetic basis for it and so there are people with certain genetic variants at a higher risk. So this study was looking at, what does Agent Orange do? They found that Agent Orange, independently, also increases the risk for some of these lymphoid cancers. They wanted to then see if both having a genetic risk and exposure to Agent Orange, does it increase that risk. And interestingly they found that it's not additive, so they're both acting independently, potentially through different biological mechanisms. Of course, it needs further research and to see what those biological pathways are and that could lead to new treatments.
Can this research provide personalized medical care to veterans?
We are moving in that direction. It takes a lot of additional work from a research discovery to go into clinical application. And so typically you have a discovery of finding, and that's an associated finding, a genetic marker is associated with a particular health condition, a disease. It doesn't mean necessarily that it's causative. So then you have to prove that it's actually causing the condition, and then how is it causing it? You have to validate that mechanism. And then you go on to this really increasing the risks, so can we develop a screening tool to identify veterans who may be at higher risk. Or does the biological mechanism tell you something about whether you can find a new treatment for this particular condition. There are different ways of doing this. The first step, if it’s treatment or even if it’s a screening tool, is doing a clinical trial.
A classic example we have is prostate cancer. We found that one of the studies generated what we call a polygenic risk order, which really means that there were a number of genetic markers together that increase the risk of metastatic prostate cancer, the lethal form of prostate cancer. What we are now doing at the VA is we have sponsored a clinical trial where we take the standard of care prostate cancer screening and then add this polygenic risk score to it. So you have cases and controls, veterans who get the standard of care, and then there are veterans who get that plus the genetic risk score added in and we're following those in a clinical trial to see if it improves. It allows us to identify veterans at risk for lethal prostate cancer sooner so you can actually treat it earlier. Over 2,000 veterans have now enrolled in that clinical trial. So that's one example of going from research towards clinical care.
And another example that you're now working on is pharmacogenomics, or the understanding of how genetics impacts the way you respond to medication. Let’s say you give medication to 10 people and not all of them respond in the same way. Some people will respond very well. Others may not respond at all. And then there may be a population that has adverse side effects. All these differences are in part due to genetics. The VA has a very strong pharmacogenomics program already in the healthcare system so we (MVP) are partnering with them to say, if we find these new genetic markers that are telling us whether a person can be responsive or not, we want to provide that information to the clinical partners in VHA so they can use that to tailor the treatment to a particular veteran. So give a particular medication only if they are going to be responsive to it. And avoid bad side effects.
How can the genetic factor that MVP is conducting research on help with mental health treatment?
If we know how a genetic marker or a change in your genetics is resulting in a mental health condition, and typically it's not just one genetic marker it’s a combination of different genes acting together. And it's not just genetics. There's lifestyle, your medical history, your family history. So you might have inherited some things genetically. Then there’s military service, what you were exposed to in the environment, all of those things come together. So you can identify new targets for treatments if you identify a genetic marker. From genetics, you go into what are called proteins, and these are what the medications target. Once you know what protein a gene makes, then you can try to identify a chemical compound that can actually negate that bad effect.
The FDA, for example, has a database of all the chemical compounds and even ones that are already approved. So you could have a medication that's approved for one health condition but now it may be effective for another health condition for treating something else. That's called repurposing for a new condition. We found over 600 different potential possibilities of repurposing existing FDA approved medications. That’s another area that we're pursuing to identify new treatments. Then use the pharmacogenomic profiles, like I said, to see whether they will respond to a particular medication. This is very important in mental health because a lot of it is trial and error. So knowing how some genetics affect how they respond to medication will be very important. The main goal is to identify strategies for preventing or for treating.
How has your role and involvement with the MVP been rewarding?
I've been with the program since it's inception, since it was just an idea in our heads to say, can we build this program in the VA? It’s now been over 15 years, and we've come a long way from initially the focus was on enrollment and getting veterans in the program. Then we shifted to generating all the data from their biospecimens, from their health records, and then conducting the science and the research studies. Now we're at this very crucial point where we're moving towards taking these discoveries into the clinic and bringing it back to veterans and helping them. So just seeing this entire journey of coming to this point, and most importantly, the veterans, they're so altruistic.
It’s really been enriching to talk to veterans, hear about their experiences. They joined this program not just for themselves. It's really because they want to help other veterans, their brothers and sisters. They want to help future generations and their families and beyond. I think the most fulfilling part has been just seeing how altruistic they are. And now how we can take something back from what they donated, a very precious donation they made to the Million Veteran Program. We can take what we learn back to improve their health, better treatments, early prevention.
- Veterans Healthcare