Genetics of coronary artery disease: discovery, biology and clinical translation

The past decade has seen tremendous progress in understanding the genetic architecture of coronary artery disease (CAD). Khera and Kathiresan review research efforts that have improved our understanding of the genetic drivers of CAD, and discuss the promises and challenges of integrating genetic information into routine clinical practice. Coronary artery disease is the leading global cause of mortality. Long recognized to be heritable, recent advances have started to unravel the genetic architecture of the disease. Common variant association studies have linked approximately 60 genetic loci to coronary risk. Large-scale gene sequencing efforts and functional studies have facilitated a better understanding of causal risk factors, elucidated underlying biology and informed the development of new therapeutics. Moving forwards, genetic testing could enable precision medicine approaches by identifying subgroups of patients at increased risk of coronary artery disease or those with a specific driving pathophysiology in whom a therapeutic or preventive approach would be most useful.