A Genome-Wide Association Study Identifies Novel Risk Loci for Type 2 Diabetes

Nature. 2007 Feb 22;445(7130):881-5. doi: 10.1038/nature05616. Epub 2007 Feb 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cation Transport Proteins / genetics
  • Chromosomes, Human, Pair 10 / genetics
  • Chromosomes, Human, Pair 8 / genetics
  • Diabetes Mellitus, Type 2 / genetics*
  • France
  • Genetic Predisposition to Disease / genetics*
  • Genome, Human*
  • Humans
  • Linkage Disequilibrium
  • Zinc Transporter 8

Substances

  • Cation Transport Proteins
  • SLC30A8 protein, human
  • Zinc Transporter 8