Leveraging information from genetic risk scores of coronary atherosclerosis

Genome-wide association studies (GWAS) have identified ∼60 loci for coronary artery disease (CAD). Through genetic risk scores (GRSs), investigators are leveraging this genomic information to gain insights on both the fundamental mechanisms driving these associations as well as their utility in improving risk prediction. GRSs of CAD track with the earliest atherosclerosis lesions in the coronary including fatty streaks and uncomplicated raised lesions. In multiple cohort studies, they predict incident CAD events independent of all traditional and lifestyle risk factors. The incorporation of SNPs with suggestive but not genome-wide association in GWAS into GRSs often increases the strength of these associations. GRS may also predict recurrent events and identify patients most likely to respond to statins. The effect of the GRS on discrimination metrics remains modest but the minimal degree of improvement needed for clinical utility is unknown. Most novel loci for CAD identified through GWAS facilitate the formation of coronary atherosclerosis and stratify individuals based on their underlying burden of coronary atherosclerosis. GRSs may one day be routinely used in clinical practice to not only assess the risk of incident events but also to predict who will respond best to established prevention strategies.