Polygenic Risk Scores in Coronary Artery Disease and Atrial Fibrillation

Abstract

Coronary artery disease (CAD) and atrial fibrillation (AF) are two highly prevalent cardiovascular disorders that are associated with substantial morbidity and mortality. Conventional clinical risk factors for these disorders may not be identified prior to mid-adult life when pathophysiological processes are already established. A better understanding of the genetic underpinnings of disease should facilitate early detection of individuals at risk and preventative intervention. Single rare variants of large effect size that are causative for CAD, AF, or predisposing factors such as hypertension or hyperlipidaemia, may give rise to familial forms of disease. However, in most individuals, CAD and AF are complex traits in which combinations of genetic and acquired factors play a role. Common genetic variants that affect disease susceptibility have been identified by genome-wide association studies, but the predictive value of any single variant is limited. To address this issue, polygenic risk scores (PRS), comprised of suites of disease-associated common variants have been devised. In CAD and AF, incorporation of PRS into risk stratification algorithms has provided incremental prognostic information to clinical factors alone. The long-term health and economic benefits of PRS-guided clinical management remain to be determined however, and further evidence-based data are required.

Keywords: Atrial fibrillation; Coronary artery disease; Genetics; Genome-wide association studies (GWAS); Polygenic risk score; Whole Genome Sequencing (WGS); meta-genomic risk score (metaGRS).