Genomewide association studies and lipid risk factors

Abstract

Plasma concentrations of lipids and lipoproteins are well-established risk factors for atherosclerotic coronary heart disease and show substantial heritability. Identification of the genetic factors underlying such complex genetic traits, in which multiple genes and significant gene-environment interactions contribute to the variation, has been challenging. This article reviews recent findings from the first wave of genomewide association studies conducted to identify loci with common variants determining high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride levels. These studies confirmed previously known common variants in candidate genes, the existence for the first time of common variants in other candidate genes, and new, previously unsuspected loci. This review also discusses the next steps: to identify the causal functional variants at the associated loci, decipher their modes of action, and consider how this information may be translated into clinical applications.