期刊
DIABETES
卷 58, 期 1, 页码 290-295出版社
AMER DIABETES ASSOC
DOI: 10.2337/db08-1022
关键词
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资金
- National Institutes of Health [U01-DK62418]
- Juvenile Diabetes Research Foundation (JDRF) International and Genome Canada through the Ontario Genomics Institute
- Canadian Institutes of Health Research
- Cotswold Foundation
- National Institute of Diabetes and Digestive and Kidney Diseases [N01-DK-62204, R01-DK-077510]
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [N01DK062204, R01DK077510] Funding Source: NIH RePORTER
OBJECTIVE-Two recent genome-wide association (GWA) studies have revealed novel loci for type 1 diabetes, a common multifactorial disease with a strong genetic component. To fully utilize the GWA data that we had obtained by genotyping 563 type 1 diabetes probands and 1,146 control subjects, as well as 483 case subject-parent trios, using the Illumina HumanHap550 BeadChip, we designed a full stage 2 study to capture other possible association signals. RESEARCH DESIGN AND METHODS-From our existing datasets, we selected 982 markers with P < 0.05 in both GWA cohorts. Genotyping these in an independent set of 636 nuclear families with 974 affected offspring revealed 75 markers that also had P < 0.05 in this third cohort. Among these, six single nucleotide polymorphisms in five novel loci also had P < 0.05 in the Wellcome Trust Case-Control Consortium dataset and were further tested in 1,303 type 1 diabetes probands from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) plus 1,673 control subjects. RESULTS-Two markers (rs9976767 and rs3757247) remained significant after adjusting for the number of tests in this last cohort; they reside in UBASH3A (OR 1.16; combined P = 2.33 X 10(-8)) and BACH2 (1.13; combined P = 1.25 X 10(-6)). CONCLUSIONS-Evaluation of a large number of statistical GWA candidates in several independent cohorts has revealed additional loci that are associated with type 1 diabetes. The two genes at these respective loci, UBASH3A and BACH2, are both biologically relevant to autoimmunity. Diabetes 58:290-295, 2009
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