A novel susceptibility locus for type 1 diabetes on Chr12q13 identified by a genome-wide association study.
OBJECTIVE
In stage 1 of our genome-wide association (GWA) study for type 1 diabetes, one locus at 16p13 was detected (P = 1.03 x 10(-10)) and confirmed in two additional cohorts. Here we describe the results of testing, in these additional cohorts, 23 loci that were next in rank of statistical significance.


METHODS
Two independent cohorts were studied. The Type 1 Diabetes Genetics Consortium replication cohort consisted of 549 families with at least one child diagnosed with diabetes (946 total affected) and DNA from both parents. The Canadian replication cohort consisted of 364 nuclear family trios with one type 1 diabetes-affected offspring and two parents (1,092 individuals).


RESULTS
One locus at 12q13, with the highest statistical significance among the 23, was confirmed. It involves type 1 diabetes association with the minor allele of rs1701704 (P = 9.13 x 10(-10), OR 1.25 [95% CI 1.12-1.40]).


CONCLUSIONS
We have discovered a type 1 diabetes locus at 12q13 that is replicated in an independent cohort of type 1 diabetic patients and confers a type 1 diabetes risk comparable with that of the 16p13 locus we recently reported. These two loci are identical to two loci identified by the whole-genome association study of the Wellcome Trust Case-Control Consortium, a parallel independent discovery that adds further support to the validity of the GWA approach.
Hakonarson
Hakon
H
Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, PA 19104-4318, USA. hakonarson@chop.edu
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Hui-Qi
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Bradfield
Jonathan P
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Marchand
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Kim
Cecilia E
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Glessner
Joseph T
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Casalunovo
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Shayne P
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Chioma C
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Chiavacci
Rosetta M
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Robinson
Luke J
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Stanley
Charles A
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Kirsch
Susan E
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Marcella
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Dimitri S
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Struan F A
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Constantin
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D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D002896:Chromosomes, Human, Pair 6; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006681:HLA-D Antigens / Q000235:genetics; D006801:Humans; D018570:Risk Assessment
D006681:HLA-D Antigens