Abstract

The WTCCC study identified 49 SNPs putatively associated with rheumatoid arthritis at P = 1 × 10−4 − 1 × 10−5 (tier 3). Here we show that three of these SNPs, mapping to chromosome 10p15 (rs4750316), 12q13 (rs1678542) and 22q13 (rs3218253), are also associated (trend P = 4 × 10−5, P = 4 × 10−4 and P = 4 × 10−4, respectively) in a validation study of 4,106 individuals with rheumatoid arthritis and an expanded reference group of 11,238 subjects, confirming them as true susceptibility loci in individuals of European ancestry.

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Acknowledgements

We thank the Arthritis Research Campaign for their support (arc grant reference no. 17552). We would also like to acknowledge the National Health Service (NHS) Research and Development Support Fund for Guy's and St Thomas' and Lewisham NHS Trusts. We acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. We thank the YEAR consortium for allowing us access to their DNA collection. D.P. is supported by the European Community's Sixth Framework Programme Autocure funding. Information-technology support was provided by P. Steer and technical support by P. Gilbert, B. Lad and S.G. Martin. Nursing support was provided by J. Grumley, J. Shotton and C. Farrar.

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Affiliations

  1. Arthritis Research Campaign (arc) Epidemiology Unit, Stopford Building, The University of Manchester, Manchester, UK.

    • Anne Barton
    • , Wendy Thomson
    • , Xiayi Ke
    • , Steve Eyre
    • , Anne Hinks
    • , John Bowes
    • , Darren Plant
    • , Laura J Gibbons
    •  & Jane Worthington
  2. School of Medicine and Biomedical Sciences, University of Sheffield, Sheffield S10 2JF, UK.

    • Anthony G Wilson
    •  & Deborah E Bax
  3. Academic Unit of Musculoskeletal Disease, Chapel Allerton Hospital, Leeds LS7 4SA, UK.

    • Ann W Morgan
    •  & Paul Emery
  4. Clinical and Academic Rheumatology, Kings College Hospital National Health Service Foundation Trust, Denmark Hill, London SE5 9RS, UK.

    • Sophia Steer
  5. Bone Research Group, Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen AB25 2ZD, UK.

    • Lynne Hocking
    •  & David M Reid
  6. University of Oxford Institute of Musculoskeletal Sciences, Botnar Research Centre, Oxford OX3 7LD, UK.

    • Paul Wordsworth
    •  & Pille Harrison

Consortia

  1. Wellcome Trust Case Control Consortium

    A full list of members is provided in the Supplementary Note

  2. YEAR Consortium

    A full list of members is provided in the Supplementary Note

  3. BIRAC Consortium

    A full list of members is provided in the Supplementary Note

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Contributions

A.B., W.T., X.K., S.E. and J.W. participated in the conception, design and coordination of the study, data analysis and writing of the manuscript. A.G.W., D.E.B., A.W.M., P.E., YEAR Consortium, BIRAC Consortium, S.S., L.H., D.M.R., P.W. and P.H. recruited study subjects and extracted phenotype data. S.E., A.H., L.J.G., D.P. and J.B. performed the genotyping. X.K. undertook the statistical analysis. WTCCC provided the initial data for rheumatoid arthritis cases and controls. Members of the WTCCC, BIRAC and YEAR consortium are listed in the Supplementary Note.

Corresponding author

Correspondence to Anne Barton.

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    Supplementary Text and Figures

    Supplementary Note, Supplementary Methods, Supplementary Tables 1–5, Supplementary Figure 1

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DOI

https://doi.org/10.1038/ng.218

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