Genetic architecture of coronary artery disease in the genome-wide era: implications for the emerging "golden dozen" loci

Abstract

Clinicians are well aware of family history as a risk factor for coronary artery disease (CAD) and myocardial infarction (MI). The underlying genetic architecture of CAD/MI is extremely complex and still poorly understood. Overall, the genetic heritability of CAD/MI is estimated to be near 40 to 60%. This proportion includes mainly genes that regulate known risk factors (e.g., lipid metabolism) but also genes involved in as yet unknown metabolic pathways. In the last 2 years, the systematic application of genome-wide association studies in the setting of large collaborative consortia including thousands of patients and controls has led to the identification of several new loci associated with CAD/MI. Here we review current knowledge on the emerging "top" 12 loci, that is, those showing the most consistent associations with clinical phenotypes. Although these genetic variants have little or no current predictive value of at the level of individual patients, they have the potential to disclose novel biological mechanisms involved in the pathophysiology of CAD/MI.