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A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex

Nature Genetics volume 13, pages 469–471 (1996)Cite this article

Abstract

Multiple sclerosis (MS), an inflammatory autoimmune demyelinating disorder of the central nervous system, is the most common cause of acquired neurological dysfunction arising in the second to fourth decades of life1,2. A genetic component to MS is indicated by an increased relative risk of 20–40 to siblings compared to the general population (γs)3–6, and an increased concordance rate in monozygotic compared to dizygotic twins7. Association and/or linkage studies to candidate genes have produced many reports of significant genetic effects including those for the major histocompatability complex (MHC; particularly the HLA-DR2 allele), immunoglobulin heavy chain (IgH), T-cell receptor (TCR) and myelin basic protein (MBP) loci8–17. With the exception of the MHC, however, these results have been difficult to replicate and/or apply beyond isolated populations. We have therefore conducted a two-stage, multi-analytical genomic screen to identify genomic regions potentially harbouring MS susceptibility genes. We geno-typed 443 markers and 19 such regions were identified. These included the MHC region on 6p, the only region with a consistently reported genetic effect. However, no single locus generated overwhelming evidence of linkage. Our results suggest that a multifactorial aetiology, including both environmental and multiple genetic factors of moderate effect, is more likely than an aetiology consisting of simple mendelian disease gene(s)

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Author notes

  1. M.A. PericakVance, E. Seboun and S.L. Hauser: J.L.H., M.A.P.-V, E.S. and S.L.H. contributed equally to this work.

Authors and Affiliations

  1. Molecular Neurogenetics Unit, Massachusetts General Hospital, Boston, Massachusetts, 02129, USA

    J.L. Haines, M. Ter-Minassian, A. Bazyk, J.F. Gusella, D.J. Kim & H. Terwedow

  2. Division of Neurology, Departments of Medicine and Genetics, Duke University Medical Center, Durham, North Carolina, 27710, USA

    M.A. PericakVance, J.B. Rimmler, C.S. Haynes, A.D. Roses, A. Lee, B. Shaner & M. Menold

  3. Gentthon, Evry, France

    E. Seboun, R-P. Fitoussi, C. Gartioux, C. Reyes, F. Ribierre, G. Gyapay & J. Weissenbach

  4. Department of Neurology, University of California, San Francisco, California, 94143, USA

    S.L. Hauser, D.E. Goodkin, R. Lincoln, K. Usuku, A. Garcia-Merino, N. Gatto, S. Young & J.R. Oksenberg

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Haines, J., Ter-Minassian, M., Bazyk, A. et al. A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex. Nat Genet 13, 469–471 (1996). https://doi.org/10.1038/ng0896-469

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