TITLE

A genome-wide association study identifies novel risk loci for type 2 diabetes

AUTHOR(S)
Sladek, Robert; Rocheleau, Ghislain; Rung, Johan; Dina, Christian; Lishuang Shen; 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
PUB. DATE
February 2007
SOURCE
Nature;2/22/2007, Vol. 445 Issue 7130, p881
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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 β-cells, and two linkage disequilibrium blocks that contain genes potentially involved in β-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.
ACCESSION #
24110168

 

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