Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

Nat Genet. 2010 Jul;42(7):579-89. doi: 10.1038/ng.609.

Abstract

By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P<5x10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.

Publication types

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

MeSH terms

  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / genetics*
  • Dual-Specificity Phosphatases / genetics
  • Fasting / blood
  • Gene Dosage
  • Gene Expression Profiling
  • Genetic Heterogeneity
  • Genetic Predisposition to Disease / genetics*
  • Genome, Human / genetics*
  • Genome-Wide Association Study
  • Hepatocyte Nuclear Factor 1-alpha / genetics
  • Humans
  • KCNQ1 Potassium Channel / genetics
  • Meta-Analysis as Topic
  • Mitogen-Activated Protein Kinase Phosphatases / genetics
  • Polymorphism, Single Nucleotide*

Substances

  • Blood Glucose
  • HNF1A protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • KCNQ1 Potassium Channel
  • Mitogen-Activated Protein Kinase Phosphatases
  • DUSP9 protein, human
  • Dual-Specificity Phosphatases

Grant support