A novel susceptibility locus for type 1 diabetes on chr12q13 identified by a genome-wide association study

Abstract

OBJECTIVE-In stage 1 of our genome-wide association (GWA) study for type 1 diabetes, one locus at 16p13 was detected (P = 1.03 × 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. RESEARCH DESIGN AND 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 × 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 wholegenome association study of the Wellcome Trust Case-Control Consortium, a parallel independent discovery that adds further support to the validity of the GWA approach.© 2008 by the American Diabetes Association.