Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease

Rationale: Coronary artery disease (CAD) is a complex phenotype driven by genetic and environmental factors. Ninety-seven genetic risk loci have been identified to date, but the identification of additional susceptibility loci might be important to enhance our understanding of the genetic architecture of CAD.

Objective: To expand the number of genome-wide significant loci, catalog functional insights, and enhance our understanding of the genetic architecture of CAD.

Methods and Results: We performed a genome-wide association study in 34541 CAD cases and 261984 controls of UK Biobank resource followed by replication in 88192 cases and 162544 controls from CARDIoGRAMplusC4D. We identified 75 loci that replicated and were genome-wide significant (P

Conclusions: We identified 64 novel genetic risk loci for CAD and performed fine mapping of all 161 risk loci to obtain a credible set of causal variants. The large expansion of reconstituted gene sets argues in favor of an expanded omnigenic model view on the genetic architecture of CAD.