Genetics of type 2 diabetes in European populations

Type 2 diabetes (T2D) has become a leading health problem throughout the world. It is caused by environmental and genetic factors, as well as interactions between the two. However, until very recently, the T2D susceptibility genes have been poorly understood. During the past 5 years, with the advent of genome-wide association studies (GWAS), a total of 58 T2D susceptibility loci have been associated with T2D risk at a genome-wide significance level (P < 5 x 10-8), with evidence showing that most of these genetic variants influence pancreatic beta-cell function. Most novel T2D susceptibility loci were identified through GWAS in European populations and later confirmed in other ethnic groups. Although the recent discovery of novel T2D susceptibility loci has contributed substantially to our understanding of the pathophysiology of the disease, the clinical utility of these loci in disease prediction and prognosis is limited. More studies using multi-ethnic meta-analysis, geneenvironment interaction analysis, sequencing analysis, epigenetic analysis, and functional experiments are needed to identify new susceptibility T2D loci and causal variants, and to establish biological mechanisms.