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A novel susceptibility locus for type 1 diabetes on Chr12q13 identified by a genome-wide association study

¹Center for Applied Genomics, and
²Department of Pathology and Laboratory Medicine, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
³Department of Pediatrics and Division of Human Genetics, and
⁴Division of Endocrinology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
⁵Departments of Pediatrics and Human Genetics, McGill University, Montreal H3H 1P3, Québec, Canada
⁶Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada
⁷Division of Endocrinology, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada
⁸Markham-Stouffville Hospital, Markham, Ontario, Canada
⁹Department of Pediatrics University of Pennsylvania, School of Medicine Philadelphia, Pennsylvania 19104, USA
¹⁰Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA

Objective: In Stage 1 of our genome-wide association (GWA) study for type 1 diabetes (T1D), one locus at 16p13 was detected (P=1.03x10^–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 (T1DGC) 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 T1D-affected offspring and two parents (1092 individuals).

Results: One locus at 12q13, with the highest statistical significance among the 23, was confirmed. It involves T1D association with the minor allele of rs1701704 (P=9.13x10^–10, OR=1.25, 95% CI=1.12, 1.40).

Conclusions: We have discovered a T1D locus at 12q13 which replicates in an independent cohort of T1D patients, and confers a comparable risk to T1D as the 16p13 locus we recently reported. These two loci are identical to two loci identified by the WGA study of the Wellcome Trust Case-Control Consortium, a parallel independent discovery that adds further support to the validity of the GWA approach.

Correspondence: constantin.polychronakos{at}mcgill.ca

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