Mapping candidate non-MHC susceptibility regions to multiple sclerosis

Genes Immun. 2006 Sep;7(6):494-502. doi: 10.1038/sj.gene.6364320. Epub 2006 Jul 13.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chromosome Mapping*
  • Female
  • Genetic Predisposition to Disease*
  • Genome, Human
  • Humans
  • Male
  • Microsatellite Repeats
  • Multiple Sclerosis / genetics*
  • Polymerase Chain Reaction