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Cited by 353Multiple Sclerosis Research StudiesGenetic Associations and EpidemiologyPsoriasis: Treatment and Pathogenesis

Genome‐wide meta‐analysis identifies novel multiple sclerosis susceptibility loci

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Patsopoulos, Nikolaos A., the Bayer Pharma MS Genetics Working Group, the Steering Committees of Studies Evaluating IFNβ‐1b and a CCR1‐Antagonist, ANZgene Consortium, GeneMSA, International Multiple Sclerosis Genetics Consortium, de Bakker, Paul I. W.·2011·Annals of Neurology
DOI 10.1002/ana.22609PMC PMC3247076
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Abstract

Objective: To perform a 1‐stage meta‐analysis of genome‐wide association studies (GWAS) of multiple sclerosis (MS) susceptibility and to explore functional consequences of new susceptibility loci. Methods: We synthesized 7 MS GWAS. Each data set was imputed using HapMap phase II, and a per single nucleotide polymorphism (SNP) meta‐analysis was performed across the 7 data sets. We explored RNA expression data using a quantitative trait analysis in peripheral blood mononuclear cells (PBMCs) of 228 subjects with demyelinating disease. Results: We meta‐analyzed 2,529,394 unique SNPs in 5,545 cases and 12,153 controls. We identified 3 novel susceptibility alleles: rs170934 T at 3p24.1 (odds ratio [OR], 1.17; p = 1.6 × 10 −8 ) near EOMES , rs2150702 G in the second intron of MLANA on chromosome 9p24.1 (OR, 1.16; p = 3.3 × 10 −8 ), and rs6718520 A in an intergenic region on chromosome 2p21, with THADA as the nearest flanking gene (OR, 1.17; p = 3.4 × 10 −8 ). The 3 new loci do not have a strong cis effect on RNA expression in PBMCs. Ten other susceptibility loci had a suggestive p < 1 × 10 −6 , some of these loci have evidence of association in other inflammatory diseases (ie, IL12B , TAGAP , PLEK , and ZMIZ1 ). Interpretation: We have performed a meta‐analysis of GWAS in MS that more than doubles the size of previous gene discovery efforts and highlights 3 novel MS susceptibility loci. These and additional loci with suggestive evidence of association are excellent candidates for further investigations to refine and validate their role in the genetic architecture of MS. ANN NEUROL 2011;70:897–912

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  • By 2011, common variants in 26 genomic loci had been associated with multiple sclerosis risk and independently replicated.

    “by 2011, common variants in 26 genomic loci had been associated with MS risk and independently replicated”

    From Genome‐wide association studies of multiple sclerosis (2018) · cites this paper as [40]

    The Introduction reports over a dozen MS susceptibility loci, and the Results discuss additional known loci. But the paper does not establish a count of 26 independently replicated loci: the Results say its findings are not independent replication evidence for IL2RA, CD58, or STAT3, and the Discussion says the new loci require replication. No page numbers are available in our copy. (LLM, conf=0.88)

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Research works printed but not linked: 33

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Cited by

Sorted by citations

Authors
Patsopoulos, N. A., the Bayer Pharma MS Genetics Working Group, T. S. C. O. S. E. I. A. A. C., & de Bakker, P. I. W.
Affiliations
Broad Institute (US)
ORCID
Patsopoulos, Nikolaos A.
Venue
Annals of Neurology
Publisher
Wiley
Published
2011-12
Volume
70
Issue
6
Pages
897-912
ISSN
  • 0364-5134 (ISSN-L)
  • 1531-8249
DOI
10.1002/ana.22609
PMC
PMC3247076
OpenAlex
W2110228129
Cited by
353
References
9
Citations by year
2026: 7 · 2025: 14 · 2024: 15 · 2023: 10 · 2022: 13 · 2021: 13 · 2020: 20 · 2019: 23 · 2018: 22 · 2017: 25 · 2016: 33 · 2015: 41 · 2014: 36 · 2013: 51 · 2012: 26
FWCI
4.68
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 20 d)
Locations
  • Annals of Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • QUT ePrints (Queensland University of Technology) (submittedVersion)
  • eCite Digital Repository (University of Tasmania) (submittedVersion)
  • UWA Profiles and Research Repository (UWA) (submittedVersion)
  • Murdoch University Research Portal (submittedVersion)
  • Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
  • Pure Amsterdam UMC (submittedVersion)
  • Griffith Research Online (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
  • National Multiple Sclerosis Society
  • John T. Reid Charitable Trusts
  • Wellcome Trust (068545/Z/02), G0000934, 068545)
  • National Institute for Health and Care Research (NF-SI-0508-10335)
  • Multiple Sclerosis Australia
  • Trish Multiple Sclerosis Research Foundation
  • National Institutes of Health (G0000934, 068545/Z/02)
  • Medical Research Council (068545/Z/02, G0000934)
  • Australian Research Council (LP0776744)
  • National Heart, Lung, and Blood Institute (068545/Z/02, G0000934)
  • National Institute of Mental Health (R01 MH61675, U01-MH79470, R01 MH-59571, R01MH59588, U01MH46276, R01-MH59566, R01-MH60879, U01MH046276, R01-MH60870, R01-MH59586, R01MH059566, R01 MH81800, R01MH59587, U01MH046318, R01-MH59565, R01MH059571, R01MH060879, R01MH059565, U01MH46289, R01MH081800, R01 MH-67257, R01MH060870, U01MH046289, U01MH079469, R01MH061675, R01MH059586, R01MH059588, R01MH067257, U01MH079470, U01MH46318, R01MH059587, U01MH-79469)
  • National Human Genome Research Institute (R01HG004960)
  • National Institute of Allergy and Infectious Diseases (P01AI039671)
  • National Institute of Neurological Disorders and Stroke (RC2NS070340, R01NS067305)
  • National Center for Research Resources
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, genetic susceptibility loci, single nucleotide polymorphisms, Eomes, THADA, peripheral blood mononuclear cells, gene expression, demyelinating disease
MeSH terms
Adolescent, Adult, Child, Disease Susceptibility, Female, Gene Frequency, Genotype, Humans, Male, Middle Aged, Multiple Sclerosis, Meta-Analysis as Topic, Odds Ratio, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Young Adult

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