Validation of a Genome-Wide Polygenic Score for Coronary Artery Disease in South Asians

Background: Genome-wide polygenic scores (GPS) integrate information from many common DNA variants into a single number. Because rates of coronary artery disease (CAD) are substantially higher among South Asians, a GPS to identify high-risk individuals may be particularly useful in this population. Objectives: We used summary statistics from a prior genome-wide association study to derive a new GPSCAD for South Asians. Methods: We validated this GPSCAD in 7,244 South Asian UK Biobank participants and tested it in 491 individuals from a case-control study in Bangladesh. Next, we built a static ancestry and GPSCAD reference distribution using whole genome sequencing from 1,522 Indian individuals, and tested a framework for projecting individuals onto this static ancestry and GPSCAD reference distribution using 1,800…