Journal article

A Polymorphism in the HLA-DPB1 Gene Is Associated with Susceptibility to Multiple Sclerosis

Judith Field, Sharon R Browning, Laura J Johnson, Patrick Danoy, Michael D Varney, Brian D Tait, Kaushal S Gandhi, Jac C Charlesworth, Robert N Heard, Graeme J Stewart, Trevor J Kilpatrick, Simon J Foote, Melanie Bahlo, Helmut Butzkueven, James Wiley, David R Booth, Bruce V Taylor, Matthew A Brown, Justin P Rubio, Jim Stankovich

PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2010

Abstract

We conducted an association study across the human leukocyte antigen (HLA) complex to identify loci associated with multiple sclerosis (MS). Comparing 1927 SNPs in 1618 MS cases and 3413 controls of European ancestry, we identified seven SNPs that were independently associated with MS conditional on the others (each P ≤ 4 x 10(-6)). All associations were significant in an independent replication cohort of 2212 cases and 2251 controls (P ≤ 0.001) and were highly significant in the combined dataset (P ≤ 6 x 10(-8)). The associated SNPs included proxies for HLA-DRB1*15:01 and HLA-DRB1*03:01, and SNPs in moderate linkage disequilibrium (LD) with HLA-A*02:01, HLA-DRB1*04:01 and HLA-DRB1*13:03. We..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by Australian Research Council


Awarded by Medical Research Council


Awarded by Wellcome Trust


Funding Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia (Project Grant number 509184, Career Development Awards to M.B., H.B. and J.P.R., Principal Research Fellowship to M. A. B.), the Australian Research Council (Linkage Project Grant number LP0776744), Multiple Sclerosis Research Australia (Linkage Project Grant, Post-doctoral Fellowship to J.F.), John T. Reid Charitable Trusts, and the Trish MS Research Foundation. J.P.R. is currently employed by GlaxoSmithKline. Genotype data from the British 1958 Birth Cohort DNA collection was funded by the Medical Research Council grant G0000934 and the Wellcome Trust Grant 068545/Z/02. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.