A Novel Susceptibility Locus for Type 1 Diabetes on Chr12q13 Identified by a Genome-Wide Association Study

  1. Constantin Polychronakos3
  1. 1Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
  2. 2Department of Pediatrics and Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
  3. 3Departments of Pediatrics and Human Genetics, McGill University, Montreal, Quebec, Canada
  4. 4Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada
  5. 5Division of Endocrinology, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada
  6. 6Division of Endocrinology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
  7. 7Markham-Stouffville Hospital, Markham, Ontario, Canada
  8. 8Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania
  9. 9Department of Pathology and Laboratory Medicine, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
  10. 10Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
  1. Address correspondence and reprint requests to Hakon Hakonarson, MD, PhD, Director, Center for Applied Genomics, 1216E Abramson Research Center, 3615 Civic Center Blvd., Philadelphia, PA 19104-4318, E-mail: hakonarson{at}; or to Constantin Polychronakos, MD, FRCPC, McGill University Health Center (Children's Hospital), 2300 Tupper, Montréal, QC, Canada, H3H 1P3, E-mail: constantin.polychronakos{at}


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 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.

  • Received September 13, 2007.
  • Accepted January 10, 2008.
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