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Mapping candidate non-MHC susceptibility regions to multiple sclerosis

Genes & Immunity volume 7, pages 494–502 (2006)Cite this article

Abstract

Understanding the genetic basis of multiple sclerosis (MS) remains a major challenge, despite decades of intensive research. In order to identify candidate non-MHC susceptibility regions to MS, the results of whole genome screens for linkage or association and follow-up studies in 18 different populations were superimposed together in a combined genomic map. Analysis of this map led to the prediction of at least 38 potential susceptibility regions, each showing linkage and/or association in several populations. Among these, 17 regions were the most reproducibly reported in these studies, thus representing top predicted candidates for MS. This non-formal approach to meta-analysis demonstrated the ability to verify results and retrieve lost information in an association study. Assessment of the map in a Northern Irish refined screen (n=415 cases, n=490 controls) revealed association in 15 regions (P<0.05), including 10 promising candidates on chromosomes 1p13, 2p13, 2q14, 3p23, 7q21, 13q14, 15q13, 17p13, 18q21 and 20p12 (P<0.0025). Seven of these regions were previously overlooked in the Northern Irish whole genome association study. Collating results from numerous studies, this draft map represents a tool that should facilitate the analysis of the genetic backgrounds of MS in many populations.

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Acknowledgements

We thank all participants for contributing DNA samples to the study. This work was supported by MS Ireland.

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Authors and Affiliations

  1. Regional Genetics Centre, Belfast City Hospital, Belfast, UK

    H Abdeen & C A Graham

  2. Genomics Core Facility, Queen's University, Belfast, UK

    S Heggarty

  3. Department of Neurology, Royal Victoria Hospital, Belfast, UK

    S A Hawkins & G V McDonnell

  4. School of Clinical Medicine, Queen's University, Belfast, UK

    S A Hawkins

  5. Department of Neurology, St Vincent's Hospital, Dublin, Ireland

    M Hutchinson

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  1. H Abdeen
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  6. C A Graham
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Correspondence to C A Graham.

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Abdeen, H., Heggarty, S., Hawkins, S. et al. Mapping candidate non-MHC susceptibility regions to multiple sclerosis. Genes Immun 7, 494–502 (2006). https://doi.org/10.1038/sj.gene.6364320

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