Linkage and association with the NOS2A locus on chromosome 17q11 in multiple sclerosis

Lisa F. Barcellos, Ann B. Begovich, Rebecca L. Reynolds, Stacy J. Caillier, David Brassat, Silke Schmidt, Sarah E. Grams, Karen Walker, Lori L. Steiner, Bruce A.C. Cree, Althea Stillman, Robin R. Lincoln, Margaret A. Pericak-Vance, Jonathan L. Haines, Henry A. Erlich, Stephen L. Hauser, Jorge R. Oksenberg

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)793-800
Number of pages8
JournalAnnals of neurology
Issue number6
StatePublished - Jun 2004
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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