Genome-Wide Association Study of Over One Million Participants Identifies 49 Novel Loci Associated With Coronary Artery Disease

Genome-wide association studies (GWAS) have identified 164 common genetic loci associated with coronary artery disease (CAD), providing important biological and clinical insights, but the global burden of CAD remains high. Additional genetic discovery may further our understanding of CAD and related conditions and improve approaches to disease management. We performed GWAS and meta-analysis of CAD in 1,165,680 individuals across cohort studies, biobanks, and clinical trials (EPIC-CVD, HUNT, deCODE, GerMIFS, UK Biobank, Partners Biobank, Greek CAD, PEGASUS-TIMI 54, SAVOR-TIMI 53, ENGAGE-TIMI 48), as well as CARDIoGRAMplusC4D. Study-specific GWAS were performed by logistic regression or generalized mixed models. Conditional and joint analyses were used to identify independent genetic signals. We developed a genome-wide polygenic risk score (PRS) and tested it in the …