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Genome-wide association study of severity in multiple sclerosis.

Publication ,  Journal Article
International Multiple Sclerosis Genetics Consortium,
Published in: Genes Immun
December 2011

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system with a strong genetic component. Several lines of evidence support a strong role for genetic factors influencing both disease susceptibility and clinical outcome in MS. Identification of genetic variants that distinguish particular disease subgroups and/or predict a severe clinical outcome is critical to further our understanding of disease mechanisms and guide development of effective therapeutic approaches. We studied 1470 MS cases and performed a genome-wide association study of more than 2.5 million single-nucleotide polymorphisms to identify loci influencing disease severity, measured using the MS severity score (MSSS), a measure of clinical disability. Of note, no single result achieved genome-wide significance. Furthermore, variants within previously confirmed MS susceptibility loci do not appear to influence severity. Although bioinformatic analyses highlight certain pathways that are over-represented in our results, we conclude that the genetic architecture of disease severity is likely polygenic and comprised of modest effects, similar to what has been described for MS susceptibility, to date. However, a role for major effects of rare variants cannot be excluded. Importantly, our results also show the MSSS, when considered as a binary or continuous phenotype variable is by comparison a stable outcome.

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Published In

Genes Immun

DOI

EISSN

1476-5470

Publication Date

December 2011

Volume

12

Issue

8

Start / End Page

615 / 625

Location

England

Related Subject Headings

  • Severity of Illness Index
  • Polymorphism, Single Nucleotide
  • Multiple Sclerosis
  • Male
  • Immunology
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female
  • 3204 Immunology
 

Citation

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ICMJE
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International Multiple Sclerosis Genetics Consortium, . (2011). Genome-wide association study of severity in multiple sclerosis. Genes Immun, 12(8), 615–625. https://doi.org/10.1038/gene.2011.34
International Multiple Sclerosis Genetics Consortium, Randall Scott. “Genome-wide association study of severity in multiple sclerosis.Genes Immun 12, no. 8 (December 2011): 615–25. https://doi.org/10.1038/gene.2011.34.
International Multiple Sclerosis Genetics Consortium. Genome-wide association study of severity in multiple sclerosis. Genes Immun. 2011 Dec;12(8):615–25.
International Multiple Sclerosis Genetics Consortium, Randall Scott. “Genome-wide association study of severity in multiple sclerosis.Genes Immun, vol. 12, no. 8, Dec. 2011, pp. 615–25. Pubmed, doi:10.1038/gene.2011.34.
International Multiple Sclerosis Genetics Consortium. Genome-wide association study of severity in multiple sclerosis. Genes Immun. 2011 Dec;12(8):615–625.

Published In

Genes Immun

DOI

EISSN

1476-5470

Publication Date

December 2011

Volume

12

Issue

8

Start / End Page

615 / 625

Location

England

Related Subject Headings

  • Severity of Illness Index
  • Polymorphism, Single Nucleotide
  • Multiple Sclerosis
  • Male
  • Immunology
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female
  • 3204 Immunology