Coronary Artery Disease Risk Loci, Candidate Genes Identified in GWAS Meta-Analysis

For a paper in Nature Genetics, a team from Massachusetts General Hospital, the Broad Institute, the University of Cambridge, and elsewhere present findings from a large coronary artery disease (CAD) genome-wide association study. With genotyping profiles for more than 210,842 cases and almost 1.2 million controls, the team initially identified 241 CAD associations, uncovering another 38 risk loci through a cross-ancestry meta-analysis. In their follow-up fine mapping and functional analyses, including CRISPR-Cas9-based gene editing experiments, the authors focused in on 220 candidate causal genes, including a Rho-GTPase-related, myosin protein-coding gene called MYO9B. "[W]e experimentally validated the effect of an enhancer in MYO9B, which appears to mediate CAD risk by regulating vascular cell motility," the authors write, noting that "experimental evidence is ultimately required to confirm causal mechanisms at all unresolved CAD risk loci."