In this interview, we speak to Dr. Sumitra Muralidhar, the Program Director for VA’s Million Veteran Program (MVP) at the U.S. Department of Veterans Affairs, about the program, what its aims are, and how it is helping to improve the lives of veterans.
Please could you introduce yourself and tell us about your role within the Million Veteran Program (MVP)?
My name is Dr. Sumitra Muralidhar, and I am the Program Director for VA’s Million Veteran Program (MVP) at the U.S. Department of Veterans Affairs. In this role, I oversee the development of policies and infrastructure as well as operations for a large, national research program on genes and health.
As the name implies, our goal is to enroll at least one million Veterans in this longitudinal genetic cohort and involves collection and research use of biospecimens and associated genetic, clinical, lifestyle, and military experiences and exposures data from our enrollees.
As Program Director, I provide overall direction and management of over 300 staff across several coordinating centers as well as more than 60 VA medical centers and over 70 community-based outpatient clinics. I also lead policy development, fiscal management, regulatory affairs, public relations, and scientific direction for the program.
The MVP is a national research program. Please can you tell us a little more about the program and what its aims are?
The Million Veteran Program is the world’s largest healthcare system-based program on genetics, health, lifestyle, as well as military experiences and exposures. The goal is ultimately to inform precision healthcare for our Veterans and the population at large. Since launching in 2011, more than 850,000 Veterans have participated by volunteering their genetic and health data.
The goal is to reach one million Veterans enrolled by FY23. Additionally, expanding access to MVP data to researchers within and outside the VA is critical to doing high-quality and impactful research to inform health care practices.
Image Credit: Million Veteran Program
How does the MVP work? What research projects are currently ongoing?
The Million Veteran Program, or MVP, is a voluntary research program. When Veterans join, they provide their consent and sign a HIPAA authorization allowing us to access their medical record data. They also provide a blood specimen for genetic and molecular analysis and complete surveys to augment the medical records, giving us a fuller picture of people’s health, lifestyles, and military experiences and exposures. Researchers with approved projects are able to access the information within centralized systems to research topics that are important to health and illness in Veterans and the population at large.
To protect the privacy and confidentiality of our participants, we don’t put a person’s name, social security number, or other identifying information on our blood samples and data when it is being used for research - it is labeled with a code. However, MVP keeps personal identifying information on blood samples and health data for internal purposes; for example, if a participant wants to be removed from MVP or to recontact them in the future.
You are currently one of the largest genetic research programs in the world. How has genetics research changed over the last 10 years and how have new scientific discoveries in genetics, such as CRISPR, further advanced your research?
Genetics research has evolved from investigators working in silos on small sample sizes to sometimes rather large multidisciplinary teams working with big data sets for genetics discovery. New methodologies are now more adept at identifying structural variants and processing whole-genome sequence data, for example. They also are more effective in assessing the additive role of a large number of genetic mutations in disease risk (called polygenic risk scores).
Currently, MVP research does not involve CRISPR.
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In recent times, mental health has become more widely recognized as a hugely important aspect of health in society. How is your program involved in mental health and what role does mental health play in veterans' overall health?
The mental health and well-being of Veterans is a high priority for the VA and is a critical part of the whole health strategy. Several MVP studies are addressing the genetics of mental health conditions such as suicide risk, PTSD, depression, anxiety, substance use disorders, and initial findings have been published in high-impact scientific journals.
MVP is also launching a sub-cohort focused on mental health called MVP-MIND ( Measures Investigating Neuropsychiatric Disorders) with the goal of enrolling 50,000 Veterans with serious mental illness. This will involve the collection of more survey information that is very targeted to mental health and substance use conditions that will provide researchers with a wealth of additional information used in studies on these topics.
Women have historically been underrepresented in medical research and studies. What impact does this have on ensuring medical breakthroughs work the same for both men and women and how is MVP working to ensure women aren’t left out of medical research?
Genetic research requires large numbers of people to participate to detect small changes or differences in DNA that affect people’s health and illness. But as you mention, historically and even up to the present day, most of our data has been, and continues to be, from men.
This means there may be variations in DNA markers between men and women that we’ll miss if more women don’t participate. Only then will we have the power in numbers to better understand health conditions affecting women Veterans with the same breadth of understanding that we’re piecing together for men’s health.
This is important because we know women Veterans experience disease differently than male Veterans. Women Veterans self-report more depression and PTSD than men on our MVP surveys, they may experience heart disease and other illnesses differently, and there are other illnesses that only or predominately affect women like breast and gynecologic cancers.
Fortunately, we’re making progress. With over 80,000 women in MVP, they represent 9% of our cohort. And of those women, about 40% are from diverse racial and ethnic groups, which makes it more and more possible to look for genetic variations that impact health not just between men and women but between women from all different backgrounds.
With that said, there is still more work to be done to increase our diversity beyond sex, so we can expand our research and understanding of illness in all Veterans, not simply male Veterans over the age of 60 of European descent, who represent the majority of our current cohort.
One example is an MVP study that was recently published on breast cancer.
Using MVP data, researchers were able to validate a genetic screening tool used in the private sector for accurately predicting breast cancer risk in Veteran populations. However, the tool was developed in the private sector with data from women of mostly European descent. More diversity is needed to validate the effectiveness of this tool for women of non-European descent.
This is a real-life implication when not enough diversity in data is represented. It illustrates why diversity matters and why MVP is committed to ensuring our cutting-edge research and breakthroughs apply to Veterans of all backgrounds.
Since its launch in 2011, what have you learned about how genes affect health and illness?
The first 3-4 years were focused on establishing the infrastructure to support centralized, national recruitment and enrollment, molecular data generation and curation, curation of electronic health record data and survey data, as well as the computing infrastructure and tools for data analysis.
Scientific studies were launched in 2016, and since then over 75 peer-reviewed publications and more than 300 scientific abstracts have resulted from MVP. New genetic variants have been identified for a wide range of chronic diseases, including several new genetic variants identified for the first time in Blacks and Hispanics. This was possible thanks to nearly 150,000 Veterans of African ancestry who enrolled in MVP, as well as over 60,000 Veterans of Hispanic heritage.
In addition to our diversity, another unique feature of MVP is the large sample resulting in some of the largest genetic association studies. Highlights on specific findings can be found at Science (va.gov) and News (va.gov).
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How are the veterans who partner with MVP helping to improve the lives of other fellow veterans as well as the population as a whole?
All of the scientific knowledge that is generated from MVP research studies, and the subsequent clinical translation that results from them (such as new risk prediction algorithms or polygenic risk scores, or new treatments or repurposed drugs), may or may not happen in time to benefit the individual Veteran who participated, but their information will benefit other Veterans, and the population at large, in the years to come.
The ongoing COVID-19 pandemic has shown the impact collaboration and working together can have on research goals and scientific discoveries. How important is collaboration and teamwork to MVP?
Collaboration and teamwork are integral to MVP – you could say it’s part of our ‘DNA’! All of the MVP data are curated centrally by our core data teams and made available to approved MVP researchers. Further, studies that have common elements of interest typically collaborate in working groups rather than working in silos and duplicating efforts. Data generated from all studies(for example, newly validated phenotypes) are deposited in a central library and repurposed for future science.
MVP also collaborates with external partners. In the face of the pandemic, for example, MVP collaborated with the Human Genetics Initiative (HGI) Consortium and provided summary data from our genome-wide association analyses. MVP has established a partnership with the Department of Energy to leverage their artificial intelligence and machine learning expertise to VA and MVP’s health and genetic data. MVP is also collaborating with the National Heart, Blood, and Lung Institute’s (NHLBI’s) TOPMED (Trans-Omics for Precision Medicine) program.
We also have a robust collaboration among researchers and world-class institutions. Our clinicians and researchers work not only at VA but also at some of the world’s most prestigious research institutions such as Harvard University, Duke University, and Stanford University.
What can veterans do to get involved?
Joining MVP is relatively easy and involves:
- Filling out surveys by mail or online about health and lifestyle
- Providing a blood sample for genetic analysis
- Allowing MVP researchers secure access to health records on an ongoing basis
- Agreeing to future contact by MVP for additional research opportunities
More information can be found at mvp.va.gov.
MVP Informational Video 2020
For yourself personally, why do you enjoy being a part of MVP?
For me, the most humbling part of this journey has been meeting Veterans and hearing their stories. Veterans of all ages, backgrounds, and creeds share with me the same message. They consider joining MVP as a second opportunity to serve their country and help their fellow service members and Veterans. I take this personally and pledge to every Veteran my full commitment to make their service in MVP count.
What are the next steps for MVP and its research?
I see two significant areas of expansion for MVP in the coming years. The first is to increase underrepresented populations in MVP, such as women, as well as racial and ethnic minorities so that the knowledge gained will apply broadly to all people. The second is to bridge the gap between research and clinical care so that we take scientific discoveries from MVP into the clinic to help Veterans and all people.
My hope is that over the next 10 to 20 years, doctors will have information not only about Veterans’ health and health history, but also their genetic profiles, lifestyle, as well as military experiences and exposures. Providers will be able to tell patients what illnesses they are at risk for, and what drugs work best for them based on their unique biology and background. The Veteran standard of care will be revolutionary – tailored and custom fit for every patient. It will be the very best care in the world.
Where can readers find more information?
About Dr. Sumitra Muralidhar
Dr. Sumitra Muralidhar is the Program Director for VA’s Million Veteran Program (MVP) in the Office of Research and Development (ORD). In this role, she oversees the policy and infrastructure development for the collection and use of samples and genetic, clinical, lifestyle and military exposure data from one million Veterans. MVP is the world’s largest healthcare system-based research program on genetics, lifestyle, military exposure and health, with the goal of ultimately providing precision healthcare to our Veteran and the population at large.
Dr. Muralidhar provides overall direction and management of the national program across sixty plus VA medical centers, seventy plus community-based outpatient clinics, operational leadership, coordination, implementation and oversight of all aspects of the program development and implementation, including policy development, fiscal management, regulatory affairs, public relations and scientific direction. She serves as the principal VA/ Million Veteran Program representative for interactions with other federal agencies, industry, Congress and the White House Office of Science and Technology Policy.
Since 2019, Sumitra is also serving as Director, VA/ORD-Department of Energy (DOE) Joint Research Programs, directing data analysis with VA/MVP data on DOE’s high-performance computers.
Prior to this, 2006-2015, Sumitra served as the Senior Scientific Program Manager in the Biomedical Laboratory Research and Development Service in ORD, where she managed several scientific portfolios and programs, including Genomics, Epidemiology, and Clinical Trials, and led the implementation of the Million Veteran Program. From 2014-2015, she served as ORD’s liaison to the White House Precision Medicine Initiative under President Obama and continues to represent ORD/MVP in the federal interagency group on precision medicine. She also served as the designated federal officer for VA’s Genomic Medicine Program Advisory Committee, which advises the VA Secretary on the development and implementation of research and clinical arms within the Veterans Health Administration from 2006-2018.
From 2005-2006, Dr. Muralidhar served as Health and Science Advisor to the Senate Veterans Affairs Committee (SVAC), where she provided oversight of VA research, including genomic medicine and mental health care for Veterans. She began her career in the VA as a Scientific Portfolio Manager in ORD in 2001. Previously, from 1996-2001, she was an Associate Professor at Georgetown University. She received her Ph.D. in Molecular Biology from the University of Maryland.