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

doi:10.1002/ana.20092

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 journal › Article › peer-review

52 Scopus citations

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.

Original language	English (US)
Pages (from-to)	793-800
Number of pages	8
Journal	Annals of neurology
Volume	55
Issue number	6
DOIs	https://doi.org/10.1002/ana.20092
State	Published - Jun 2004
Externally published	Yes

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1002/ana.20092

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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., & Oksenberg, J. R. (2004). Linkage and association with the NOS2A locus on chromosome 17q11 in multiple sclerosis. Annals of neurology, 55(6), 793-800. https://doi.org/10.1002/ana.20092

Linkage and association with the NOS2A locus on chromosome 17q11 in multiple sclerosis. / 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.; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Erlich, Henry A.; Hauser, Stephen L.; Oksenberg, Jorge R.

In: Annals of neurology, Vol. 55, No. 6, 06.2004, p. 793-800.

Research output: Contribution to journal › Article › peer-review

Barcellos, LF, Begovich, AB, Reynolds, RL, Caillier, SJ, Brassat, D, Schmidt, S, Grams, SE, Walker, K, Steiner, LL, Cree, BAC, Stillman, A, Lincoln, RR, Pericak-Vance, MA, Haines, JL, Erlich, HA, Hauser, SL & Oksenberg, JR 2004, 'Linkage and association with the NOS2A locus on chromosome 17q11 in multiple sclerosis', Annals of neurology, vol. 55, no. 6, pp. 793-800. https://doi.org/10.1002/ana.20092

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. ; Pericak-Vance, Margaret A. ; Haines, Jonathan L. ; Erlich, Henry A. ; Hauser, Stephen L. ; Oksenberg, Jorge R. / Linkage and association with the NOS2A locus on chromosome 17q11 in multiple sclerosis. In: Annals of neurology. 2004 ; Vol. 55, No. 6. pp. 793-800.

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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.",

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AU - Brassat, David

AU - Schmidt, Silke

AU - Grams, Sarah E.

AU - Walker, Karen

AU - Steiner, Lori L.

AU - Cree, Bruce A.C.

AU - Stillman, Althea

AU - Lincoln, Robin R.

AU - Pericak-Vance, Margaret A.

AU - Haines, Jonathan L.

AU - Erlich, Henry A.

AU - Hauser, Stephen L.

AU - Oksenberg, Jorge R.

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

Abstract

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