Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20

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To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13–14 (rs703842, P = 5.4 × 10−11; rs10876994, P = 2.7 × 10−10; rs12368653, P = 1.0 × 10−7) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 × 10−7; rs1569723, P = 2.9 × 10−7). Both loci are also associated with other autoimmune diseases1,2,3,4,5. We also replicated several known MS associations (HLA-DR15, P = 7.0 × 10−184; CD58, P = 9.6 × 10−8; EVI5-RPL5, P = 2.5 × 10−6; IL2RA, P = 7.4 × 10−6; CLEC16A, P = 1.1 × 10−4; IL7R, P = 1.3 × 10−3; TYK2, P = 3.5 × 10−3) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).

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Figure 1: Chromosome 12q13–14 region and association with MS.
Figure 2: Chromosome 20q13 region and association with MS.

Change history

  • 24 November 2009

    In the version of this article initially published, the 8th SNP in Table 3 was incorrectly listed as rs8118449. The correct identification number for this SNP is rs8112449. The error has been corrected in the HTML and PDF versions of the article.


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We thank individuals with MS in Australia and New Zealand for supporting this research. We are grateful to M. Tanner for database management and J. Wright and C. Remediakis from Multiple Sclerosis Research Australia (MSRA) for expediting this research. J.P.R. and M.B. are supported by Career Development Awards from The National Health and Medical Research Council of Australia (NHMRC). M.A.B. is an NHMRC Principal Research Fellow. H.B. is an NHMRC Peter Doherty Post-doctoral Fellow. J.F. is an MSRA Post-doctoral Fellow. M.B.C. is supported by a grant from the John Hunter Hospital Charitable Trust Fund and a special grant from Macquarie Bank. Replication genotyping was conducted at the Murdoch Children's Research Institute Sequenom Platform Facility. This work was supported by MSRA, John T. Reid Charitable Trusts, Trish MS Research Foundation and the Australian Research Council, under the Linkage Projects Scheme (LP0776744).

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Correspondence to Justin P Rubio or (Chair) Justin P Rubio or Justin P Rubio.

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Supplementary Tables 1–5, Supplementary Figures 1–3 and Supplementary Note (PDF 754 kb)

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