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A genome screen in multiple sclerosis reveals susceptibility loci on chromosome 6p21 and 17q22

Nature Genetics volume 13, pages 464–468 (1996)Cite this article

Abstract

The population prevalence of multiple sclerosis is 0.1 %1; however, the risk of the disease in the siblings of affected individuals is very much higher at 3–5%2,3. The importance2 of genetic factors in accounting for this increased risk is confirmed by the results of twin and adoption studies4–7. Despite the evidence for a strong genetic effect, a weak major histocompatibility complex (MHC) association is the only consistently observed feature in the genetics of multiple sclerosis8–11. Other candidates have been proposed, including genes encoding the immunoglobulin heavy chain12–14, T cell receptor β chain15,16 and APOC217, but none has yet been confirmed18,19. Evidence for linkage and association to the myelin basic protein gene has been reported in a genetically isolated Finnish population20, but it has not been possible to reproduce these results in other populations21,22. We used a two-stage approach to search the human genome for the genes causing susceptibility to multiple sclerosis. Two principal regions of linkage are identified, chromosomes 17q22 and 6p21 (MHC). Our results are compatible with genetic models involving epistatic interaction between these and several additional genes.

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Authors and Affiliations

  1. University of Cambridge Neurology unit, Addenbrooke's Hospital, Hills Road, Cambridge, CB22QQ, UK

    Stephen Sawcer, Robert Feakes, Julia Gray, Jeremy Chataway, Neil Robertson & Alastair Compston

  2. Department of Genetics, University of Cambridge, Downing Street, Cambridge, CB2 3EH, UK

    Stephen Sawcer, Hywel B. Jones, Robert Feakes, Niki Smaldon & Peter N. Goodfellow

  3. MRC Biostatistics Unit, Institute of PublicHealth, University Forvie Site, Robinson Way, Cambridge, CB2 2SR, UK

    David Clayton

  4. MRC Cambridge Centre for Brain Repair, University Forvie Site, Robinson Way, Cambridge, CB2 2SR, UK

    Alastair Compston

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  1. Stephen Sawcer
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Correspondence to Stephen Sawcer.

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Sawcer, S., Jones, H., Feakes, R. et al. A genome screen in multiple sclerosis reveals susceptibility loci on chromosome 6p21 and 17q22. Nat Genet 13, 464–468 (1996). https://doi.org/10.1038/ng0896-464

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