Most genetic studies focus on people of European descent, limiting understanding of how genes influence health in other populations. Researchers at the University of Pennsylvania’s Perelman School of Medicine and the Corporal Michael J. Crescenz Veterans Affairs Medical Center have partnered with a team of researchers from the Department of Veterans Affairs and the Department of Energy’s Oak Ridge and Argonne National Laboratories to conduct large-scale studies with diverse groups to better understand the genetic factors that influence health and disease. The Million Veterans Program (MVP), for example, includes people from diverse backgrounds along with their detailed medical histories. A study published this month in Science They analyzed genetic data from 635,969 veterans and 2,069 traits and identified a total of 26,049 associations between specific genetic variants and various traits or health conditions.
The study, one of the largest of its kind, used data from MVP, a longitudinal study of U.S. war veterans, in which more than 29% of participants were of non-European descent. The researchers identified 13,672 specific regions of DNA that are associated with one or more traits, such as physical characteristics or health conditions. These regions, known as genetic risk areas, can influence a person’s likelihood of having certain traits or developing certain diseases.
“Understanding the genetic factors underlying health disparities is crucial to developing targeted interventions and treatments that can benefit all people, regardless of their background,” said the study’s corresponding author, Dr. Scott Damrauer, associate professor of Genetics at Penn and vascular surgeon at Crescenz VA. “By uncovering these genetic insights in diverse populations, we are taking important steps toward a more personalized and inclusive approach to health care.”
Specifically, the study found population-specific signals, such as the rs72725854 variant at the PCAT2 locus associated with prostate cancer risk, predominantly seen in African-American men. It also revealed a novel gout risk variant, rs35965584, in the African-American population group, along with the known variant rs2231142.
The study showed that the genetics of most traits are similar across diverse groups of people, but that certain groups have their own distinctive genetic characteristics. They were able to find these differences more accurately, especially in African American and mixed-ancestry groups, thanks to improvements in the way DNA is analyzed, such as fine mapping, which allows researchers to identify the exact genetic changes responsible for a particular trait or condition. The findings highlight the importance of including diverse genetic backgrounds to understand the genetic causes of health disparities.
“Our work demonstrates that there are far more similarities than differences in genetic associations across groups,” said first author Anurag Verma, MD, assistant professor of Translational Medicine and Human Genetics and an investigator in the VA MVP program. “However, the unique genetic variations identified in diverse populations provide critical insights into health disparities and have significant implications for precision medicine.”
“Biobanks like MVP serve as a critical resource for generating new insights and knowledge about genetic associations. The findings from this inclusive and diverse study lay the groundwork for future genetic research that will first and foremost help us better care for our nation’s veterans, as well as their families, caregivers, survivors, and other non-veterans. This was only possible because of the selflessness and diversity of the participating veterans,” said VA MVP Program Director Sumitra Muralidhar, PhD.
The study was funded by the U.S. Department of Veterans Affairs’ Office of Research and Development.