Coronary Artery Disease Genetics Enlightened by Genome-Wide Association Studies

Many cardiovascular diseases are facilitated by strong inheritance. For example, large-scale genetic studies identified hundreds of genomic loci that affect the risk of coronary artery disease. At each of these loci, common variants are associated with disease risk with robust statistical evidence but individually small effect sizes. Only a minority of candidate genes found at these loci are involved in the pathophysiology of traditional risk factors, but experimental research is making progress in identifying novel, and, in part, unexpected mechanisms. Targets identified by genome-wide association studies have already led to the development of novel treatments, specifically in lipid metabolism. This review summarizes recent genetic and experimental findings in this field. In addition, the development and possible clinical usefulness of polygenic risk scores in risk prediction and individualization of treatment, particularly in lipid metabolism, are discussed. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Automated summary

Many cardiovascular diseases have a strong genetic component, with large-scale genetic studies identifying genomic loci that influence the risk of specific diseases. While most candidate genes at these loci are not traditionally associated with disease risk factors, experimental research is uncovering novel and unexpected mechanisms. Genome-wide association studies have already led to the development of new treatments, particularly in lipid metabolism. Additionally, polygenic risk scores may have clinical utility in risk prediction and personalized treatment, especially in lipid metabolism.