Clinical utility of polygenic risk scores for coronary artery disease

• Published in: Nature reviews cardiology Vol. 19; no. 5; pp. 291 - 301
• Main Authors: Klarin, Derek, Natarajan, Pradeep
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.05.2022
• Subjects: Algorithms; Cardiovascular disease; Clinical medicine; Clinical trials; Coronary Artery Disease - diagnosis; Coronary Artery Disease - drug therapy; Coronary Artery Disease - genetics; Coronary vessels; Genetic Predisposition to Disease; Humans; Multifactorial Inheritance; Prospective Studies; Risk Factors; Vein & artery diseases
• ISSN: 1759-5002; 1759-5010
• DOI: 10.1038/s41569-021-00638-w

Over the past decade, substantial progress has been made in the discovery of alleles contributing to the risk of coronary artery disease. In addition to providing causal insights into disease, these endeavours have yielded and enabled the refinement of polygenic risk scores. These scores can be used to predict incident coronary artery disease in multiple cohorts and indicate the clinical response to some preventive therapies in post hoc analyses of clinical trials. These observations and the widespread ability to calculate polygenic risk scores from direct-to-consumer and health-care-associated biobanks have raised many questions about responsible clinical adoption. In this Review, we describe technical and downstream considerations for the derivation and validation of polygenic risk scores and current evidence for their efficacy and safety. We discuss the implementation of these scores in clinical medicine for uses including risk prediction and screening algorithms for coronary artery disease, prioritization of patient subgroups that are likely to derive benefit from treatment, and efficient prospective clinical trial designs.