From GWAS to new biology and treatments in CAD

Coronary artery disease (CAD), which remains a leading cause of mortality worldwide [1], is caused by the development of atherosclerotic plaques in the arterial wall. Disease risk is influenced by environmental and lifestyle factors as well as having a significant genetic component. Over the last decade, genome-wide association studies (GWAS) have revealed the chromosomal loci contributing to increased CAD susceptibility, with the most recent investigation linking more than 300 genetic variants to disease [2]. A key characteristic of these loci is that most do not work through traditional CAD risk factors and current treatment targets such as plasma LDL-cholesterol levels or blood pressure. Importantly, for the majority of loci the underlying mechanism is unknown suggesting that our knowledge of disease pathogenesis is far from complete. CAD loci therefore offer a resource for the understanding of the molecular pathways and biological processes driving disease and potential identification of therapeutic targets.