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Analysis of 55 autoimmune disease and type II diabetes loci: further confirmation of chromosomes 4q27, 12q13.2 and 12q24.13 as type I diabetes loci, and support for a new locus, 12q13.3–q14.1

Genes & Immunity volume 10, pages S95–S120 (2009)Cite this article

Abstract

A candidate gene study was conducted on 10 established type II diabetes genes and 45 genes associated with autoimmune diseases, including type I diabetes (T1D), in a maximum of 1410 affected sib-pair families assembled by the Type I Diabetes Genetics Consortium. Associations at P values <10−3 were found for three known T1D regions at chromosomes 4q27, 12q13.2 and 12q24.13 (http://www.T1DBase.org). Support was obtained for a newly identified T1D candidate locus on chromosome 12q13.3–12q14.1 (rs1678536/KIF5A: P=8.1 × 10−3; relative risk (RR) for minor allele=0.89, 95% CI=0.82–0.97), which has a separate association from the previously reported T1D candidate locus ERBB3/12q13.2–q13.3. Our new evidence adds to that previously published for the same gene region in a T1D case–control study (rs1678542; P=3.0 × 10−4; odds ratio (OR)=0.92, 95% CI=0.88–0.96). This region, which contains many genes, has also been associated with rheumatoid arthritis.

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Acknowledgements

The Type I Diabetes Genetics Consortium is a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Allergy and Infectious Diseases (NIAID), the National Human Genome Research Institute (NHGRI), the National Institute of Child Health and Human Development (NICHD) and supported by U01 DK062418. JDC, NMW, DJS, KD, BCH and JAT are funded by the Juvenile Diabetes Research Foundation International (JDRF), the Wellcome Trust and the National Institute for Health Research Cambridge Biomedical Centre. The Cambridge Institute for Medical Research is in receipt of a Wellcome Trust Strategic Award (079895). Genotyping was performed at the Broad Institute Center for Genotyping and Analysis is supported by grant U54 RR020278 from the National Center for Research Resources.

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  1. Department of Medical Genetics, Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK

    J D Cooper, N M Walker, B C Healy, D J Smyth, K Downes & J A Todd

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  1. J D Cooper
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Correspondence to J D Cooper.

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Cooper, J., Walker, N., Healy, B. et al. Analysis of 55 autoimmune disease and type II diabetes loci: further confirmation of chromosomes 4q27, 12q13.2 and 12q24.13 as type I diabetes loci, and support for a new locus, 12q13.3–q14.1. Genes Immun 10 (Suppl 1), S95–S120 (2009). https://doi.org/10.1038/gene.2009.98

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