A genome-wide association study identifies novel risk loci for type 2 diabetes by Sladek Robert, Rocheleau Ghislain, Rung Johan, Dina Christian, Shen Lishuang, Serre David, Boutin Philippe, Vincent Daniel, Belisle Alexandre, Hadjadj Samy, Balkau Beverley, Heude Barbara, Charpentier Guillaume, Hudson Thomas J, Montpetit Alexandre, Pshezhetsky Alexey V, Prentki Marc, Posner Barry I, Balding David J, Meyre David, Polychronakos Constantin, Froguel Philippe in Nature (2007).

[PMID: 17293876] PubMed


Type 2 diabetes mellitus results from the interaction of environmental factors with a combination of genetic variants, most of which were hitherto unknown. A systematic search for these variants was recently made possible by the development of high-density arrays that permit the genotyping of hundreds of thousands of polymorphisms. We tested 392,935 single-nucleotide polymorphisms in a French case-control cohort. Markers with the most significant difference in genotype frequencies between cases of type 2 diabetes and controls were fast-tracked for testing in a second cohort. This identified four loci containing variants that confer type 2 diabetes risk, in addition to confirming the known association with the TCF7L2 gene. These loci include a non-synonymous polymorphism in the zinc transporter SLC30A8, which is expressed exclusively in insulin-producing beta-cells, and two linkage disequilibrium blocks that contain genes potentially involved in beta-cell development or function (IDE-KIF11-HHEX and EXT2-ALX4). These associations explain a substantial portion of disease risk and constitute proof of principle for the genome-wide approach to the elucidation of complex genetic traits.

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