Genomic reflections of coronary artery disease.

Coronary artery disease (CAD) is a multistaged process leading to a wide spectrum of pathoanatomic and clinical presentations.1 Given the diversity of underlying mechanisms, it is reasonable to involve distinct genetic modifiers along the cascade of events. Yet, molecular genetic association studies usually admix patients with stable and acute presentation, stenotic and ectatic forms of CAD, as well as proximal, distal or bifurcational lesions. In this issue of Circulation: Cardiovascular Genetics, Kitsios et al2 address this issue by analyzing the impact of phenotype heterogeneity on the strength of association at previously identified risk loci for CAD. Perhaps surprisingly, the authors found little evidence for a contribution of phenotype definition to between-study heterogeneity of association signals at already known genomic CAD loci.