Genome-wide Association Study and Meta-Analysis Find That Over 40 Loci Affect Risk of Type 1 Diabetes

Nat Genet. 2009 Jun;41(6):703-7. doi: 10.1038/ng.381. Epub 2009 May 10.

Abstract

Type 1 diabetes (T1D) is a common autoimmune disorder that arises from the action of multiple genetic and environmental risk factors. We report the findings of a genome-wide association study of T1D, combined in a meta-analysis with two previously published studies. The total sample set included 7,514 cases and 9,045 reference samples. Forty-one distinct genomic locations provided evidence for association with T1D in the meta-analysis (P < 10(-6)). After excluding previously reported associations, we further tested 27 regions in an independent set of 4,267 cases, 4,463 controls and 2,319 affected sib-pair (ASP) families. Of these, 18 regions were replicated (P < 0.01; overall P < 5 × 10(-8)) and 4 additional regions provided nominal evidence of replication (P < 0.05). The many new candidate genes suggested by these results include IL10, IL19, IL20, GLIS3, CD69 and IL27.

Publication types

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

MeSH terms

  • Algorithms
  • Antigens, CD / genetics
  • CTLA-4 Antigen
  • Chromosome Mapping / methods*
  • Chromosomes, Human, Pair 1 / genetics
  • Chromosomes, Human, Pair 17 / genetics
  • Chromosomes, Human, Pair 2 / genetics
  • DEAD-box RNA Helicases / genetics
  • DNA / genetics
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology
  • Family
  • Female
  • Genome-Wide Association Study*
  • Genotype
  • HLA Antigens / genetics
  • Humans
  • Interferon-Induced Helicase, IFIH1
  • Male
  • Meta-Analysis as Topic*
  • Polymorphism, Single Nucleotide / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics
  • Risk Assessment
  • Siblings

Substances

  • Antigens, CD
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • HLA Antigens
  • DNA
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22
  • IFIH1 protein, human
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1