Multi-ancestry genome-wide analysis identifies effector genes and druggable pathways for coronary artery calcification

Abstract

AbstractCoronary artery calcification (CAC), a measure of subclinical atherosclerosis, predicts symptomatic coronary artery disease. Identifying genetic risk factors for CAC may point to new therapeutic avenues for preventing clinical disease. Here, we conducted a multi-ancestry genome-wide association study in 26,909 individuals of European ancestry and 8,867 individuals of African American ancestry. We identified 11 independent risk loci, of which 8 are novel for CAC. Some novel loci harbor candidate causal genes supported by multiple lines of functional evidence. Together, these findings help refine the genetic architecture of CAC, extend our understanding of the biological pathways underlying CAC formation, as well as identify druggable targets for CAC.