title: Genetic susceptibility to MS: a second stage analysis in Canadian MS families.
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.
authors.affiliation: The Wellcome Trust Center for Human Genetics, Oxford, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Dyment
authors.forename: C J
authors.initials: CJ
authors.lastname: Willer
authors.forename: B
authors.initials: B
authors.lastname: Scott
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authors.lastname: Armstrong
authors.forename: A
authors.initials: A
authors.lastname: Ligers
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authors.initials: J
authors.lastname: Hillert
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authors.initials: DW
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authors.lastname: Hashimoto
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authors.lastname: Devonshire
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authors.lastname: Kastrukoff
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authors.initials: L
authors.lastname: Metz
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authors.lastname: Warren
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authors.lastname: Hader
authors.forename: C
authors.initials: C
authors.lastname: Power
authors.forename: A
authors.initials: A
authors.lastname: Auty
authors.forename: A
authors.initials: A
authors.lastname: Nath
authors.forename: R
authors.initials: R
authors.lastname: Nelson
authors.forename: M
authors.initials: M
authors.lastname: Freedman
authors.forename: D
authors.initials: D
authors.lastname: Brunet
authors.forename: J E
authors.initials: JE
authors.lastname: Paulseth
authors.forename: G
authors.initials: G
authors.lastname: Rice
authors.forename: P
authors.initials: P
authors.lastname: O'Connor
authors.forename: P
authors.initials: P
authors.lastname: Duquette
authors.forename: Y
authors.initials: Y
authors.lastname: Lapierre
authors.forename: G
authors.initials: G
authors.lastname: Francis
authors.forename: J P
authors.initials: JP
authors.lastname: Bouchard
authors.forename: T J
authors.initials: TJ
authors.lastname: Murray
authors.forename: V
authors.initials: V
authors.lastname: Bhan
authors.forename: C
authors.initials: C
authors.lastname: Maxner
authors.forename: W
authors.initials: W
authors.lastname: Pryse-Phillips
authors.forename: M
authors.initials: M
authors.lastname: Stefanelli
authors.forename: A D
authors.initials: AD
authors.lastname: Sadovnick
authors.forename: N
authors.initials: N
authors.lastname: Risch
authors.forename: G C
authors.initials: GC
authors.lastname: Ebers
mesh_terms: D002170:Canada; D005190:Family; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D009679:Nuclear Family; D012984:Software
chemical_list: D005819:Genetic Markers; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains