Linkage disequilibrium screening for multiple sclerosis implicates JAG1 and POU2AF1 as susceptibility genes in Europeans

J Neuroimmunol. 2006 Oct;179(1-2):108-16. doi: 10.1016/j.jneuroim.2006.06.003. Epub 2006 Aug 24.

Abstract

By combining all the data available from the Genetic Analysis of Multiple sclerosis in EuropeanS (GAMES) project, we have been able to identify 17 microsatellite markers showing consistent evidence for apparent association. As might be expected five of these markers map within the Major Histocompatibility Complex (MHC) and are in LD with HLA-DRB1. Individual genotyping of the 12 non-MHC markers confirmed association for three of them--D11S1986, D19S552 and D20S894. Association mapping across the candidate genes implicated by these markers in 937 UK trio families revealed modestly associated haplotypes in JAG1 (p=0.019) on chromosome 20p12.2 and POU2AF1 (p=0.003) on chromosome 11q23.1.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium-Binding Proteins / genetics*
  • Europe / epidemiology
  • Female
  • Genetic Predisposition to Disease*
  • Genetic Testing*
  • Genotype
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Jagged-1 Protein
  • Linkage Disequilibrium / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Microsatellite Repeats
  • Multiple Sclerosis / epidemiology
  • Multiple Sclerosis / genetics*
  • Serrate-Jagged Proteins
  • Trans-Activators / genetics*

Substances

  • Calcium-Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jagged-1 Protein
  • Membrane Proteins
  • POU2AF1 protein, human
  • Serrate-Jagged Proteins
  • Trans-Activators