A genome-wide association study identifies novel risk loci for type 2 diabetes Academic Article uri icon

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  • 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.


  • 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 Jean-Claude
  • Polychronakos, Constantin
  • Froguel, Philippe

publication date

  • February 2007