Genome-wide association studies of late-onset cardiovascular disease. (June 2015)

• Record Type: Journal Article
• Authors: Smith, J.Gustav; Newton-Cheh, Christopher
• Is Part Of: Journal of molecular and cellular cardiology. Volume 83(2015:Jun.)
• Page Start: 131
• Page End: 141
• Publication Date: 2015-06
• Subjects: Genome-wide association study -- Cardiovascular disease -- Aging; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2015.04.004
• Languages: English
• ISSNs: 0022-2828

Abstract

Abstract: Human genetics is a powerful tool for discovering causal mediators of human disease and physiology. Cardiovascular diseases with late onset in the lifecourse have historically not been considered genetic diseases, but in recent years the contribution of a heritable factor has been established. More importantly, over the last decade genome-wide association studies (GWASs) have identified many loci associated with late-onset cardiovascular diseases including coronary artery disease, carotid artery disease, ischemic stroke, aortic aneurysm, peripheral vascular disease, atrial fibrillation, valvular disease and correlates of vascular and myocardial function. Here we review findings from GWASs considered statistically robust with regard to multiple testing (p < 5 × 10 − 8 ) for late-onset cardiovascular diseases and traits. Although for only a handful of the 92 genetic loci described here have the mechanisms underlying disease association been established, new and previously unsuspected pathways have been implicated for several conditions. Examples include a role for NO signaling in myocardial repolarization and sudden cardiac death and a role for the protein sortilin in lipid metabolism and coronary artery disease. Genetic loci with multiple trait associations have also provided novel biological insights. For example, of the 46 genetic loci associated with coronary artery disease, only 16 are also associated with conventional risk factors for cardiovascular disease whereas the remaining two thirds may reflect novel pathways. Much work remains to functionally characterize genetic loci and for clinical utility, but accruing insights into the biological basis of cardiovascular aging in human populations promise to point to novel therapeutic and preventive strategies. This article is part of a Special Issue entitled 'SI:CV Aging'. Highlights: A genetic component to late-onset cardiovascular diseases has been established. GWAS has identified many loci contributing to risk of late-onset CVD. We summarize loci identified with a stringent statistical significance threshold. Only for a few loci have mechanisms explaining CVD association been described. Mechanistic insights hold promise for novel therapeutic and preventive strategies.