Future use of genomics in coronary artery disease

Abstract

Coronary artery disease (CAD) remains the number one cause of death in industrialized countries despite our collective efforts to minimize attributable risk from known contributors to CAD such as hypertension, dyslipidemia, and smoking. In addition, clinical trials have consistently demonstrated a family history of coronary disease to be predictive for future cardiovascular events beyond that which would be explained by traditional risk factors. These findings support and have prompted widespread investigation into the genomic basis of CAD and myocardial infarction (MI). Recent advances in genotyping technology have allowed for easier identification and confirmation of susceptibility genes for complex traits across different cohorts via increased power of studies stemming from faster accrual of cases and control subjects and more precise genetic mapping. These technological advances have resulted in defining the genes contributing to a substantial or even majority of population-attributable risk for type 2 diabetes and age-related macular degeneration (AMD) cases. Similar progress in replicating novel susceptibility genes for CAD and specifically MI is now rapidly occurring, with a recent gene marker on chromosome 9p21 representing a highly significant and common variant susceptibility factor. With improved resequencing technology and better phenotypic characterization of our CAD cases and control subjects, we should achieve successes in gene identification and confirmation similar to diabetes and AMD, thereby allowing us to better quantify CAD risk earlier in life and institute more effective therapy reducing the individual propensity to develop CAD.