Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

Nat Genet. 2012 Sep;44(9):981-90. doi: 10.1038/ng.2383. Epub 2012 Aug 12.

Abstract

To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genes / physiology
  • Genetic Predisposition to Disease* / genetics
  • Genome-Wide Association Study / statistics & numerical data*
  • Humans
  • Linkage Disequilibrium
  • Male
  • Pakistan / epidemiology
  • Polymorphism, Single Nucleotide / physiology
  • Sex Factors

Grant support