title: Linkage and association with the NOS2A locus on chromosome 17q11 in multiple sclerosis.
abstract: A large body of research supports a multifactorial cause in multiple sclerosis (MS), with an underlying genetic susceptibility likely acting in concert with undefined environmental exposures. Here, we used a highly efficient multilocus genotyping assay to study single nucleotide polymorphisms representing variation in 34 genes from inflammatory pathways in a well-characterized MS familial data set. Evidence of transmission distortion was present for several polymorphisms. Results for the NOS2A locus (exon 10 C/T, D346D) on chromosome 17q11 remained significant after correction for multiple testing and were reproduced in a second independent African American MS data set. In addition, linkage to a NOS2A promoter region polymorphism, (CCTTT)(n), was present in a third data set of multicase MS families. Our results provide strong evidence for linkage and association to a new candidate disease gene on chromosome 17q11 in MS and suggest that variation within NOS2A or a nearby locus contributes to disease susceptibility.
authors.affiliation: Department of Neurology, School of Medicine, University of California at San Francisco, San Francisco, CA 94143-0435, USA.
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Barcellos
authors.forename: Ann B
authors.initials: AB
authors.lastname: Begovich
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Reynolds
authors.forename: Stacy J
authors.initials: SJ
authors.lastname: Caillier
authors.forename: David
authors.initials: D
authors.lastname: Brassat
authors.forename: Silke
authors.initials: S
authors.lastname: Schmidt
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Grams
authors.forename: Karen
authors.initials: K
authors.lastname: Walker
authors.forename: Lori L
authors.initials: LL
authors.lastname: Steiner
authors.forename: Bruce A C
authors.initials: BA
authors.lastname: Cree
authors.forename: Althea
authors.initials: A
authors.lastname: Stillman
authors.forename: Robin R
authors.initials: RR
authors.lastname: Lincoln
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.forename: Henry A
authors.initials: HA
authors.lastname: Erlich
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hauser
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Oksenberg
mesh_terms: D000328:Adult; D001741:Black or African American; D016022:Case-Control Studies; D002886:Chromosomes, Human, Pair 17; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015802:HLA-DR2 Antigen; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D015802:HLA-DR2 Antigen; D019001:Nitric Oxide Synthase