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Follow-up of 1715 SNPs from the Wellcome Trust Case Control Consortium genome-wide association study in type I diabetes families

Genes & Immunity volume 10, pages S85–S94 (2009)Cite this article

Abstract

The advent of genome-wide association (GWA) studies has revolutionized the detection of disease loci and provided abundant evidence for previously undetected disease loci that can be pooled together in meta-analysis studies or used to design follow-up studies. A total of 1715 SNPs from the Wellcome Trust Case Control Consortium GWA study of type I diabetes (T1D) were selected and a follow-up study was conducted in 1410 affected sib-pair families assembled by the Type I Diabetes Genetics Consortium. In addition to the support for previously identified loci (PTPN22/1p13; ERBB3/12q13; SH2B3/12q24; CLEC16A/16p13; UBASH3A/21q22), evidence supporting two new and distinct chromosome locations associated with T1D was observed: FHOD3/18q12 (rs2644261, P=5.9 × 10−4) and Xp22 (rs5979785, P=6.8 × 10−3; http://www.T1DBase.org). There was independent support for both SNPs in a GWA meta-analysis of 7514 cases and 9045 controls (P values=5.0 × 10−3 and 6.7 × 10−6, respectively). The chromosome 18q12 region contains four genes, none of which are obvious functional candidate genes. In contrast, the Xp22 SNP is located 30 kb centromeric of the functional candidate genes TLR8 and TLR7 genes. Both TLR8 and TLR7 are functional candidate genes owing to their key roles as pathogen recognition receptors and, in the case of TLR7, overexpression has been associated directly with murine autoimmune disease.

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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 the Infectious Diseases (NIAID), the National Human Genome Research Institute (NHGRI), the National Institute of Child Health and the Human Development (NICHD), Juvenile Diabetes Research Foundation International (JDRF) and supported by U01 DK062418. JDC, NMW, DJS, KD, BCH and JAT are funded by the the Juvenile Diabetes Research Foundation International, 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, D J Smyth, K Downes, B C Healy & 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., Smyth, D. et al. Follow-up of 1715 SNPs from the Wellcome Trust Case Control Consortium genome-wide association study in type I diabetes families. Genes Immun 10 (Suppl 1), S85–S94 (2009). https://doi.org/10.1038/gene.2009.97

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