Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.
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.
Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Jeffrey C
JC
Barrett
David G
DG
Clayton
Patrick
P
Concannon
Beena
B
Akolkar
Jason D
JD
Cooper
Henry A
HA
Erlich
Cécile
C
Julier
Grant
G
Morahan
Jørn
J
Nerup
Concepcion
C
Nierras
Vincent
V
Plagnol
Flemming
F
Pociot
Helen
H
Schuilenburg
Deborah J
DJ
Smyth
Helen
H
Stevens
John A
JA
Todd
Neil M
NM
Walker
Stephen S
SS
Rich
D000465:Algorithms; D015703:Antigens, CD / Q000235:genetics; D060908:CTLA-4 Antigen; D002874:Chromosome Mapping / Q000379:methods*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics; D004247:DNA / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D005190:Family; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D008297:Male; D015201:Meta-Analysis as Topic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics; D018570:Risk Assessment; D035781:Siblings
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006680:HLA Antigens; D004247:DNA; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1