Genetic susceptibility to MS: A second stage analysis in Canadian MS families

David A. Dyment, Cristen J. Willer, Beverly Scott, Holly Armstrong, Arturs Ligers, Jan Hillert, Donald W. Paty, Stanley Hashimoto, Virginia Devonshire, John Hooge, Lorne Kastrukoff, Joel Oger, Luanne Metz, Sharon Warren, Walter Hader, Cristopher Power, Anthony Auty, Avindra Nath, Robert Nelson, Mark FreedmanDonald Brunet, John E. Paulseth, George Rice, Paul O'Connor, Pierre Duquette, Yves Lapierre, Gordon Francis, Jean Pierre Bouchard, T. John Murray, Virender Bhan, Charles Maxner, William Pryse-Phillips, Mark Stefanelli, A. Dessa Sadovnick, Neil Risch, George C. Ebers

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Four published genome screens have identified a number of markers with increased sharing in multiple sclerosis (MS) families, although none has reached statistical significance. One hundred and five markers previously identified as showing increased sharing in Canadian, British, Finnish, and American genome screens were genotyped in 219 sibling pairs ascertained from the database of the Canadian Collaborative Project on Genetic Susceptibility to MS (CCPGSMS). No markers examined met criteria for significant linkage. Markers located at 5p14 and 17q22 were analyzed in a total of 333 sibling pairs and attained mlod scores of 2.27 and 1.14, respectively. The known HLA Class II DRB1 association with MS was confirmed (P<0.0001). Significant transmission disequilibrium was also observed for D17S789 at 17q22 (P=0.0015). This study highlights the difficulty of searching for genes with only mild-to-moderate effects on susceptibility, although large effects of specific loci may still be present in individual families. Future progress in the genetics of this complex trait may be helped by (1) focussing on more ethnically homogeneous samples, (2) using an increased number of MS families, and (3) using transmission disequilibrium analysis in candidate regions rather than the affected relative pair linkage analysis.

Original languageEnglish (US)
Pages (from-to)145-151
Number of pages7
JournalNeurogenetics
Volume3
Issue number3
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Linkage analysis
  • Multiple sclerosis
  • Susceptibility loci

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Cellular and Molecular Neuroscience

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