Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Nature, 2007-02, Vol.445 (7130), p.881-885

Ort / Verlag

London: Nature Publishing

Erscheinungsjahr

2007

Quelle

Psychology and Behavioral Sciences Collection

Beschreibungen/Notizen

• 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.