Emerging Genomic Applications in Coronary Artery Disease

Over the last 4 years, an unprecedented number of studies illuminating the genomic underpinnings of common “polygenic” diseases including coronary artery disease have been published. Notably, these studies have established numerous deoxyribonucleic acid (DNA) variants within or near chromosome 9p21.3, the LPA, CXADR, and APOE genes, to name a few, as key coronary artery disease and sudden cardiac death susceptibility markers. Most importantly, many of these DNA variants confer over a 2-fold increase in risk for coronary artery disease, myocardial infarction, and ventricular fibrillation. Additionally, loss-of-function variants in the hepatic cytochrome 2C19 system have now been found to be the predominant genetic mediators of clopidogrel antiplatelet response, with variant carriers having a >3-fold increase in risk for stent thrombosis. In the near future, many additional rare polymorphisms, structural variants, and tissue-specific epigenetic features of the human genome including DNA methylation, histone modifications, and chromatin state will emerge as significant contributors to disease pathogenesis and drug response. In aggregate, these findings will have the potential to radically change the practice of cardiovascular medicine. However, only the individual clinician can ultimately enable the translation of these important discoveries to systematic implementation in clinical practice.