Further novel type 2 diabetes loci uncovered

30 June 2010

Type 2 diabetes (T2D) is a common life-long condition where the level of blood glucose is too high, either because the body cannot produce enough insulin (which is needed for glucose to enter the body’s cells) or the insulin that is produced does not function properly. To date, several genes have been confirmed as being involved in T2D, along with many more common variants associated at the genome-wide significance level (see previous news). But despite all this research, less than 10 percent of the overall estimated genetic contribution to T2D predisposition is accounted for.

A new study published in the journal Nature Genetics has identified further novel loci, increasing the number of confirmed loci for T2D to 38. The study, performed by researchers from the across the world, combined data from over 40,000 T2D cases and almost 100,000 controls all of European descent [Voight et al. Nature Genetics (2010) doi:10.1038/ng.609]. The results from eight genome-wide association studies involving 8,130 cases and 38,987 controls were combined using a meta-analysis. After removing SNPs located near previously identified genes, the 23 most strongly associated autosomal SNPs were followed-up in a further 19 studies comprising of up to around 34,000 cases and 60,000 controls. An X chromosome signal was also followed up in 4 studies involving 8,500 cases and 12,000 controls. The researchers then combined both stages in a further meta-analysis, with 14 loci (13 autosomal and 1 X chromosome) reaching genome-wide significance. Two loci represent associations already reported in subsets of the data leaving twelve loci for further investigation, of which nine represent truly novel associations. The new loci include genes involved in beta-cell function, insulin action and cell cycle regulation.

Comment: It is becoming increasingly evident that common SNPs are not going to fully explain the heritability of common complex diseases; even including these new loci only, the genetic risk variants association with T2D only account for a small fraction of the disease. This suggests that elusive rare genetic variants may be playing a larger role. Interestingly, a number of loci associated with T2D susceptibility have also been implicated in other common traits, suggesting an overlapping and hitherto unsuspected shared genetic architecture.

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