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Linkage and association with the NOS2A locus on chromosome 17q11 in multiple sclerosis
Author(s) -
Barcellos Lisa F.,
Begovich Ann B.,
Reynolds Rebecca L.,
Caillier Stacy J.,
Brassat David,
Schmidt Silke,
Grams Sarah E.,
Walker Karen,
Steiner Lori L.,
Cree Bruce A. C.,
Stillman Althea,
Lincoln Robin R.,
PericakVance Margaret A.,
Haines Jonathan L.,
Erlich Henry A.,
Hauser Stephen L.,
Oksenberg Jorge R.
Publication year - 2004
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20092
Subject(s) - genetics , biology , locus (genetics) , genotyping , linkage disequilibrium , single nucleotide polymorphism , genetic linkage , candidate gene , genetic association , genotype , gene
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. Ann Neurol 2004