Cited by 120Multiple Sclerosis Research StudiesGenetic Associations and EpidemiologyPsoriasis: Treatment and Pathogenesis

Genome-wide association study of severity in multiple sclerosis

Open access
International Multiple Sclerosis Genetics Consortium, Briggs, Farren B S, Shao, Xiaorong, Goldstein, Benjamin A, Oksenberg, Jorge R, Barcellos, Lisa F, De Jager, Philip L·2011·Genes & Immunity

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/gene.2011.34

Cites

65 of 65 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Published efforts to systematically interrogate MS severity have only involved modest numbers of cases and have not identified any convincingly associated genetic variants.

    “published efforts to systematically interrogate severity have, thus far, only involved modest numbers of cases, and unanimously fall short of identifying any convincingly associated genetic variants5,10,11.”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
International Multiple Sclerosis Genetics Consortium, Briggs, F. B. S., Shao, X., Goldstein, B. A., Oksenberg, J. R., Barcellos, L. F., & De Jager, P. L.
Venue
Genes & Immunity
Published
2011-06-09
Volume
12
Issue
8
Pages
615-625
ISSN
  • 1466-4879 (ISSN-L)
  • 1476-5470
OpenAlex
W32848451
Cited by
120
References
65
Citations by year
2026: 3 · 2025: 6 · 2024: 4 · 2023: 6 · 2022: 8 · 2021: 12 · 2020: 5 · 2019: 11 · 2018: 9 · 2017: 6 · 2016: 8 · 2015: 4 · 2014: 9 · 2013: 13 · 2012: 12
FWCI
8.55
Type
journal article
Language
en
Open access
Locations
  • Genes and Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Wellcome Trust (084702/Z/08/Z)
  • Ministère de la Santé et des Services sociaux
  • National Institute for Health and Care Research
  • National Institutes of Health
  • National Institute of Mental Health (T32MH065215, MH065215)
  • National Institute of Allergy and Infectious Diseases (AI076544, R01AI076544)
  • National Institute of Neurological Disorders and Stroke (NS067305, NS032830, NS049477, R01NS032830, R01NS067305, R01NS049477)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords
multiple sclerosis, disease severity, clinical disability, genetic susceptibility loci, polygenic architecture, rare variants, single nucleotide polymorphisms, disease outcome prediction, gene pathways
MeSH terms
Female, Humans, Male, Multiple Sclerosis, Severity of Illness Index, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review