title: Multiple sclerosis susceptibility-associated SNPs do not influence disease severity measures in a cohort of Australian MS patients.
abstract: Recent association studies in multiple sclerosis (MS) have identified and replicated several single nucleotide polymorphism (SNP) susceptibility loci including CLEC16A, IL2RA, IL7R, RPL5, CD58, CD40 and chromosome 12q13-14 in addition to the well established allele HLA-DR15. There is potential that these genetic susceptibility factors could also modulate MS disease severity, as demonstrated previously for the MS risk allele HLA-DR15. We investigated this hypothesis in a cohort of 1006 well characterised MS patients from South-Eastern Australia. We tested the MS-associated SNPs for association with five measures of disease severity incorporating disability, age of onset, cognition and brain atrophy. We observed trends towards association between the RPL5 risk SNP and time between first demyelinating event and relapse, and between the CD40 risk SNP and symbol digit test score. No associations were significant after correction for multiple testing. We found no evidence for the hypothesis that these new MS disease risk-associated SNPs influence disease severity.
authors.affiliation: Howard Florey Institute, Melbourne, Australia.
authors.forename: Cathy J
authors.initials: CJ
authors.lastname: Jensen
authors.forename: Jim
authors.initials: J
authors.lastname: Stankovich
authors.forename: Anneke
authors.initials: A
authors.lastname: Van der Walt
authors.forename: Melanie
authors.initials: M
authors.lastname: Bahlo
authors.forename: Bruce V
authors.initials: BV
authors.lastname: Taylor
authors.forename: Ingrid A F
authors.initials: IA
authors.lastname: van der Mei
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Foote
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Kilpatrick
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Johnson
authors.forename: Ella
authors.initials: E
authors.lastname: Wilkins
authors.forename: Judith
authors.initials: J
authors.lastname: Field
authors.forename: Patrick
authors.initials: P
authors.lastname: Danoy
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
authors.forename: Justin P
authors.initials: JP
authors.lastname: Rubio
authors.forename: Helmut
authors.initials: H
authors.lastname: Butzkueven
mesh_terms: D000328:Adult; D017668:Age of Onset; D001284:Atrophy; D001315:Australia; D001921:Brain / Q000473:pathology; D003071:Cognition; D015331:Cohort Studies; D004185:Disability Evaluation; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index