Coronary Artery Disease Genetics Enlightened by Genome-Wide Association Studies
Thorsten Kessler, Heribert Schunkert
Abstract
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.