A genome-wide association study identifies novel risk loci for type 2 diabetes - PubMed (original) (raw)

. 2007 Feb 22;445(7130):881-5.

doi: 10.1038/nature05616. Epub 2007 Feb 11.

Ghislain Rocheleau, Johan Rung, Christian Dina, Lishuang Shen, David Serre, Philippe Boutin, Daniel Vincent, Alexandre Belisle, Samy Hadjadj, Beverley Balkau, Barbara Heude, Guillaume Charpentier, Thomas J Hudson, Alexandre Montpetit, Alexey V Pshezhetsky, Marc Prentki, Barry I Posner, David J Balding, David Meyre, Constantin Polychronakos, Philippe Froguel

Affiliations

• PMID: 17293876
• DOI: 10.1038/nature05616

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

Robert Sladek et al. Nature. 2007.

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 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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Comment in

• Human genetics: variants in common diseases.
  Freimer NB, Sabatti C. Freimer NB, et al. Nature. 2007 Feb 22;445(7130):828-30. doi: 10.1038/nature05568. Nature. 2007. PMID: 17293879 No abstract available.

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