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The new $38-million National Institutes of Health consortium – led at UNC-Chapel Hill by Yun Li, PhD – will develop better ways to use polygenic risk scores in diverse communities as estimates for an individual’s risk of developing specific diseases.

The National Institutes of Health (NIH) will fund grants totaling $38 million over five years to develop methods to improve the way polygenic risk scores can be used to predict disease in diverse communities. Polygenic risk scores (PRS) are a genetic estimate of a person’s risk for specific diseases. Researchers and clinicians calculate polygenic risk scores by comparing the genomic data of people with and without a particular disease.

The National Human Genome Research Institute (NHGRI), part of NIH, will fund five awards for $33 million, while the National Cancer Institute (NCI) will fund one award for $5 million.

At UNC-Chapel Hill, Yun Li, PhD, professor in the UNC Department of Genetics, will lead a project titled Polygenic risk scores and health disparities: the role of blood cells immune response and evolutionary adaptation. Her award is for more than $4.9 million over five years. Li, who holds a joint faculty appointment at the UNC Gillings School of Global Public Health, is the principle investigator and is joined by several researchers, including Laura Raffield, PhD, and Daniel Schrider, PhD, both assistant professors of genetics at the UNC School of Medicine.

Research shows that early approaches to calculating polygenic risk scores, which were developed using data from mostly European ancestry populations, are not effective when used in diverse populations.

The new consortium will pool genomic information from existing and new datasets to develop and evaluate the methods used for calculating polygenic risk scores for specific diseases, with an emphasis on studying people from different ancestries. Researchers will also identify best practices to ensure that the scores accurately predict disease across diverse populations.

Researchers have used available large-scale genomic datasets to develop the ability to calculate polygenic risk scores for numerous conditions, such as coronary heart disease and diabetes, and to identify people who are at high risk. This has started to allow clinicians to use polygenic risk scores in combination with a person’s lifestyle and environmental factors to tailor their medical management.

“One of our biggest concerns is that data used to calculate polygenic risk scores do not include sufficient numbers of individuals from diverse populations, falling short of effectively predicting disease risk in non-European populations,” said Teri Manolio, MD, PhD, director of the Division of Genomic Medicine at NHGRI. “This is an area where the consortium’s work will be critical.”

The consortium will also leverage the already established NHGRI’s Genomic Data Science Analysis, Visualization and Informatics Lab-space (AnVIL) cloud-based resource to address their computational analysis and storage needs.

The newly awarded study sites will each take a unique approach to improving polygenic risk score development. Aside from the UNC-Chapel Hill site, they include: Sally Adebamowo, DSc, University of Maryland School of Medicine, Baltimore; David V. Conti, PhD, University of Southern California, Los Angeles (funded by NCI); Amit Khera, MD, Massachusetts General Hospital, Boston and Broad Institute, Cambridge; Josep Mercader, PhD, Broad Institute, Cambridge, Massachusetts; and Bogdan Pasaniuc, PhD, University of California, Los Angeles.

Read more about the consortium from the NIH.