The Review of Diabetic Studies,2008,5,3,175-179.
Several lines of evidence suggest that genetic susceptibility plays a major role in the pathogenesis of type 2 diabetes mellitus (T2DM). Limited success of candidate gene approach and linkage analysis in identifying the genetic background of T2DM has caused many research groups to apply the genome-wide association studies (GWAS) approach. Recently, several GWAS have identified and validated novel gene variants highly associated with T2DM. Unfortunately, most of the genetic variance in risk of T2DM still remains undiscovered. The main topic for discussion concerning genetics of T2DM during the 2008 EASD sessions was how to get more data from existing GWAS, and how to improve GWAS for the future. The presentations and subsequent discussions highlighted some clear weaknesses of GWAS that need to be overcome before further progress can be made. One recognized minefield is the inability to pick up the signals from true diabetes susceptibility variants, against the background statistical noise produced by a large number of other analyzed markers. Also, there are the problems of low sensitivity in identifying the signals from relatively rare variants, and the low effectiveness in identifying epistatic gene-gene interactions.