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

J. L. Haines, M. Ter-Minassian, A. Bazyk, J. F. Gusella, D. J. Kim, H. Terwedow, M. A. Pericak-Vance, J. B. Rimmler, C. S. Haynes, A. D. Roses, A. Lee, B. Shaner, M. Menold, E. Seboun, R. P. Fitoussi, C. Gartioux, C. Reyes, F. Ribierre, G. Gyapay

Research output: Contribution to journalArticlepeer-review

600 Scopus citations

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 life. A genetic component to MS is indicated by an increased relative risk of 20-40 to siblings compared to the general population (λ(s)), and an increased concordance rate in monozygotic compared to dizygotic twins. Association and/or linkage studies to candidate genes have produced many reports of significant genetic effects including those for the major histocompatibility complex (MHC; particularly the HLA-DR2 allele), immunoglobulin heavy chain (IgH), T-cell receptor (TCR) and myelin basic protein (MBP) loci. 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 genotyped 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).

Original languageEnglish (US)
Pages (from-to)469-471
Number of pages3
JournalNature genetics
Volume13
Issue number4
DOIs
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'A complete genomic screen for multiple sclerosis underscores a role for the major histocompatibility complex'. Together they form a unique fingerprint.

Cite this