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CD226 Gly307Ser association with multiple autoimmune diseases

Genes & Immunity volume 10, pages 5–10 (2009)Cite this article

Abstract

Genome-wide association studies provide insight into multigenic diseases through the identification of susceptibility genes and etiological pathways. In addition, the identification of shared variants among autoimmune disorders provides insight into common disease pathways. We previously reported an association of a nonsynonymous single nucleotide polymorphism (SNP) rs763361/Gly307Ser in the immune response gene CD226 on chromosome 18q22 with type 1 diabetes (T1D) susceptibility. Here, we report efforts toward identifying the causal variant by exonic resequencing and tag SNP mapping of the 18q22 region in both T1D and multiple sclerosis (MS). In addition to the analysis of newly available samples in T1D (2088 cases and 3289 controls) and autoimmune thyroid disease (AITD) (821 cases and 1920 controls), resulting in strong support for the Ser307 association with T1D (P=3.46 × 10−9) and continued potential evidence for AITD (P=0.0345), we provide evidence for association of Gly307Ser with MS (P=4.20 × 10−4) and rheumatoid arthritis (RA) (P=0.017). The Ser307 allele of rs763361 in exon 7 of CD226 predisposes to T1D, MS, and possibly AITD and RA, and based on the tag SNP analysis, could be the causal variant.

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Acknowledgements

We thank the Juvenile Diabetes Research Foundation, the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre and the Wellcome Trust for funding. We gratefully acknowledge the participation of all the patients and control subjects. We acknowledge use of the DNA from the British 1958 Birth Cohort collection, funded by the Medical Research Council and Wellcome Trust. We also thank The Avon Longitudinal Study of Parents and Children laboratory in Bristol and the British 1958 Birth Cohort team, including S Ring, R Jones, M Pembrey, W McArdle, D Strachan and P Burton for preparing and providing the control DNA samples. We thank Cristin Aubin at the Broad Institute. We thank Helen Schuilenburg and Nigel Ovington for data support as well as Oliver Burren for bioinformatics support. DNA samples were prepared by P Clarke, J Denesha, D Harrison, S Hawkins, M Himsworth, T Mistry, N Taylor and N Ubani. This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk. LSW is a Juvenile Diabetes Research Foundation/Wellcome Trust Principal Research Fellow. The Cambridge Institute for Medical Research is the recipient of a Wellcome Trust Strategic Award (079895).

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Authors and Affiliations

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

    J P Hafler, J D Cooper, V Plagnol, H E Stevens, N M Walker, B Healy, J M M Howson, M Maisuria, S Duley, G Coleman, L S Wicker & J A Todd

  2. Division of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA

    L M Maier & V K Kuchroo

  3. Arthritis Research Campaign (arc)-Epidemiology Unit, The University of Manchester, Manchester, UK

    A Hinks & J Worthington

  4. School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

    M J Simmonds & S C L Gough

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  1. J P Hafler
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  2. L M Maier
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  3. J D Cooper
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  4. V Plagnol
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  5. A Hinks
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  6. M J Simmonds
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  7. H E Stevens
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  8. N M Walker
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  11. M Maisuria
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  13. G Coleman
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  17. L S Wicker
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  18. J A Todd
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The International Multiple Sclerosis Genetics Consortium (IMSGC)

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Correspondence to J P Hafler.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Hafler, J., Maier, L., Cooper, J. et al. CD226 Gly307Ser association with multiple autoimmune diseases. Genes Immun 10, 5–10 (2009). https://doi.org/10.1038/gene.2008.82

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