The genetics of coronary heart disease

Abstract

Background: Coronary heart disease (CHD) is a leading cause of death worldwide, yet many areas of its pathogenesis remain unknown or poorly understood, leaving potential for novel preventive and therapeutic interventions. Recent major advances in genomic science and technology have opened new avenues of investigation in the pathogenesis of CHD, some of which are leading to clinical translation.

Sources of data: The published literature in CHD genetics has burgeoned in the last 5 years with the reporting of genome-wide association studies (GWASs) and many other findings.

Areas of agreement: Identification of many genetic variants with small effects on CHD risk has been a common finding. These have included several predicted loci, such as those involved in conventional CHD risk factors (e.g. plasma lipids) and many novel loci, where their mechanism of action is unclear. The need for large, collaborative approaches to research has also become clear and is now an accepted modus operandi.

Areas of controversy: The clinical utility of novel GWAS findings remains uncertain. In particular, the relative contribution of common variants of modest effect and rare variants of larger effects to risk of CHD or response to drugs is unclear.

Growing points: As a greater number of larger GWASs are conducted in CHD and its related phenotypes, much effort is being made to find translational applications for their findings. Therapeutics, prediction and pathology are major areas of research endeavour.