Original Article

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

  1. Lisa F. Barcellos PhD1,2,
  2. Ann B. Begovich PhD3,†,
  3. Rebecca L. Reynolds PhD3,
  4. Stacy J. Caillier BS1,
  5. David Brassat MD1,
  6. Silke Schmidt PhD4,
  7. Sarah E. Grams BS3,
  8. Karen Walker BS3,
  9. Lori L. Steiner BS3,
  10. Bruce A. C. Cree MD, PhD1,
  11. Althea Stillman BS1,
  12. Robin R. Lincoln BS1,
  13. Margaret A. Pericak-Vance PhD4,
  14. Jonathan L. Haines PhD5,
  15. Henry A. Erlich PhD3,
  16. Stephen L. Hauser MD1,
  17. Jorge R. Oksenberg PhD1,*

Article first published online: 27 APR 2004

DOI: 10.1002/ana.20092

Issue

Annals of Neurology

Annals of Neurology

Volume 55, Issue 6, pages 793–800, June 2004

Additional Information

How to Cite

Barcellos, L. F., Begovich, A. B., Reynolds, R. L., Caillier, S. J., Brassat, D., Schmidt, S., Grams, S. E., Walker, K., Steiner, L. L., Cree, B. A. C., Stillman, A., Lincoln, R. R., Pericak-Vance, M. A., Haines, J. L., Erlich, H. A., Hauser, S. L. and Oksenberg, J. R. (2004), Linkage and association with the NOS2A locus on chromosome 17q11 in multiple sclerosis. Ann Neurol., 55: 793–800. doi: 10.1002/ana.20092

Author Information

  1. 1

    Department of Neurology, School of Medicine, University of California at San Francisco

  2. 2

    Division of Epidemiology, School of Public Health, University of California at Berkeley

  3. 3

    Department of Human Genetics, Roche Molecular Systems, Inc., Alameda, CA

  4. 4

    Center for Human Genetics, Department of Medicine, Duke University Medical Center, Durham, NC

  5. 5

    Program in Human Genetics, Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN

  1. †

    Celera Diagnostics, 1401 Harbor Bay Parkway, Alameda, CA 94502

*Department of Neurology, University of California, San Francisco, 513 Parnassus Avenue, S-256, San Francisco, CA 94143-0435

Publication History

  1. Issue published online: 27 MAY 2004
  2. Article first published online: 27 APR 2004
  3. Manuscript Accepted: 17 FEB 2004
  4. Manuscript Revised: 13 FEB 2004
  5. Manuscript Received: 24 OCT 2003

Funded by

  • NIH (National Institute of Neurological Disorders and Stroke). Grant Number: NS 46297
  • NMSS (National Multiple Sclerosis Society). Grant Number: RG3060
  • Nancy Davis Foundation

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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. Ann Neurol 2004

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