Friday, May 9, 2025
5/9/2025
Leveraging pleiotropy to develop polygenic risk scores for cardiometabolic diseases - Abstract/Summary Cardiometabolic diseases (CMD) are the leading causes of death worldwide. In this application we explore the genomic risk for common CMD, including type 2 diabetes, coronary artery disease, hypertension, and dyslipidemia, across non-European ancestry populations. Recent studies have shown that these complex human traits are genetically correlated by pleiotropy, which occurs when a genetic locus affects more than one trait and is a possible underlying cause for observed cross-phenotype associations. Relative to pleiotropy, polygenic risk scores (PRS) which are estimated by combining GWAS-associated variants into a composite score, may better explain the correlation between complex traits, by determining a subset of risk variants for each outcome. However, PRS translate poorly when the discovery and target populations have differential ancestry. Combining pleiotropy and PRS has great potential to uncover novel risk variants associated with CMD. We leverage the large dataset in the All of Us research program and the NIH-funded CARdiometabolic Disorders IN African- ancestry PopuLations (CARDINAL) study site, to identify pleiotropic variants and develop PRS for type 2 diabetes, coronary artery disease, hypertension, and dyslipidemia, in populations of diverse ancestry. The All of Us dataset is ideal for generating novel biologic insights into complex disease etiology, with applications in global populations.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).