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PMID: 19430480
Published · ppublish
English
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.
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.
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,genetics,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
Chemicals
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
Investigators
382 investigators, click to expand
References (27)
27 references, click to expand
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
Published
2009-06-00
Epub
2009-00-10
Pages
703-7
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC2889014
Subset
IM
Grants
NIMH NIH HHS · MH 63420 · United States
Medical Research Council · G0000934 · United Kingdom
NIMH NIH HHS · MH059571 · United States
NIMH NIH HHS · MH067257 · United States
NIDDK NIH HHS · K08 DK002876 · United States
NIMH NIH HHS · R01 MH067257 · United States
NIMH NIH HHS · R01 MH059587 · United States
NIMH NIH HHS · MH060879 · United States
NIMH NIH HHS · R01 MH059566 · United States
NIMH NIH HHS · MH59566 · United States
Wellcome Trust · 061858 · United Kingdom
NIMH NIH HHS · MH59587 · United States
NIMH NIH HHS · R01 MH061675 · United States
NIMH NIH HHS · MH061675 · United States
NIDDK NIH HHS · R01 DK046635 · United States
NIMH NIH HHS · MH60870 · United States
NIMH NIH HHS · MH59586 · United States
NIDDK NIH HHS · DK46635 · United States
Wellcome Trust · 076113 · United Kingdom
NIMH NIH HHS · R01 MH060870 · United States
NIDDK NIH HHS · R01 DK046635-15 · United States
NIDDK NIH HHS · U01 DK062418 · United States
NIMH NIH HHS · R01 MH059571 · United States
NIMH NIH HHS · R01 MH059565 · United States
NIMH NIH HHS · MH059565 · United States
NIMH NIH HHS · R01 MH059586 · United States
NIMH NIH HHS · MH059588 · United States
NIDDK NIH HHS · U01 DK062418-06 · United States
NIMH NIH HHS · R01 MH063420 · United States
NIMH NIH HHS · R01 MH059588 · United States
NIDDK NIH HHS · K08 DK002876-06 · United States
NIMH NIH HHS · R01 MH060879 · United States
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