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. 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 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.
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. 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 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 diabeticpatients 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.
Authors: M V Prasad Linga Reddy; H Wang; S Liu; B Bode; J C Reed; R D Steed; S W Anderson; L Steed; D Hopkins; J-X She Journal: Genes Immun Date: 2011-01-27 Impact factor: 2.676
Authors: Amy Murphy; Jen-Hwa Chu; Mousheng Xu; Vincent J Carey; Ross Lazarus; Andy Liu; Stanley J Szefler; Robert Strunk; Karen Demuth; Mario Castro; Nadia N Hansel; Gregory B Diette; Becky M Vonakis; N Franklin Adkinson; Barbara J Klanderman; Jody Senter-Sylvia; John Ziniti; Christoph Lange; Tomi Pastinen; Benjamin A Raby Journal: Hum Mol Genet Date: 2010-09-10 Impact factor: 6.150
Authors: Michael L Stitzel; Praveen Sethupathy; Daniel S Pearson; Peter S Chines; Lingyun Song; Michael R Erdos; Ryan Welch; Stephen C J Parker; Alan P Boyle; Laura J Scott; Elliott H Margulies; Michael Boehnke; Terrence S Furey; Gregory E Crawford; Francis S Collins Journal: Cell Metab Date: 2010-11-03 Impact factor: 27.287
Authors: Stuart B Smith; Hui-Qi Qu; Nadine Taleb; Nina Y Kishimoto; David W Scheel; Yang Lu; Ann-Marie Patch; Rosemary Grabs; Juehu Wang; Francis C Lynn; Takeshi Miyatsuka; John Mitchell; Rina Seerke; Julie Désir; Serge Vanden Eijnden; Marc Abramowicz; Nadine Kacet; Jacques Weill; Marie-Eve Renard; Mattia Gentile; Inger Hansen; Ken Dewar; Andrew T Hattersley; Rennian Wang; Maria E Wilson; Jeffrey D Johnson; Constantin Polychronakos; Michael S German Journal: Nature Date: 2010-02-11 Impact factor: 49.962