The Genetic Association of Variants in CD6, TNFRSF1A and IRF8 to Multiple Sclerosis: A Multicenter Case-Control Study
Open accessAbstract
BACKGROUND: In the recently published meta-analysis of multiple sclerosis genome-wide association studies De Jager et al. identified three single nucleotide polymorphisms associated to MS: rs17824933 (CD6), rs1800693 (TNFRSF1A) and rs17445836 (61.5 kb from IRF8). To refine our understanding of these associations we sought to replicate these findings in a large more extensive independent sample set of 11 populations of European origin. PRINCIPAL FINDINGS: We calculated individual and combined associations using a meta-analysis method by Kazeem and Farral (2005). We confirmed the association of rs1800693 in TNFRSF1A (p 4.19 × 10-7, OR 1.12, 7,665 cases, 8,051 controls) and rs17445836 near IRF8 (p 5.35 × 10-10, OR 0.84, 6,895 cases, 7,580 controls and 596 case-parent trios) The SNP rs17824933 in CD6 also showed nominally significant evidence for association (p 2.19 × 10-5, OR 1.11, 8,047 cases, 9,174 controls, 604 case-parent trios). CONCLUSIONS: Variants in TNFRSF1A and in the vicinity of IRF8 were confirmed to be associated in these independent cohorts, which supports the role of these loci in etiology of multiple sclerosis. The variant in CD6 reached genome-wide significance after combining the data with the original meta-analysis. Fine mapping is required to identify the predisposing variants in the loci and future functional studies will refine their molecular role in MS pathogenesis.
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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 [41]
The Introduction lists multiple MS-associated loci, and the Discussion reports independent replication of variants at TNFRSF1A and near IRF8. Neither section states that common variants at 26 loci had been independently replicated by 2011; the count and its replication qualifier are unsupported. (LLM, conf=0.86)
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Non-HLA Genes and Multiple Sclerosis
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- Authors
- The International Multiple Sclerosis Genetics Consortium
- Affiliations
- Institute for Molecular Medicine Finland (FI)
- Corresponding author
- The International Multiple Sclerosis Genetics Consortium
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-04-28
- Volume
- 6
- Issue
- 4
- Pages
- e18813
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3084233
- OpenAlex
- W2106624849
- Cited by
- 74
- References
- 32
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 3 · 2022: 6 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 7 · 2015: 8 · 2014: 7 · 2013: 15 · 2012: 5
- FWCI
- 6.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Tampere University Institutional Repository (Tampere University) (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Tampere University Institutional Repository (Tampere University) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Site cant be reached (submittedVersion, cc-by)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- National Multiple Sclerosis Society
- Biogen
- Fondazione CRT
- Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques
- Strategiske Forskningsråd (2142-08-0039)
- Scleroseforeningen
- Helsingin ja Uudenmaan Sairaanhoitopiiri
- Wellcome Trust (213506, 129680, 089061, 089061/Z/09/Z)
- National Institute for Health and Care Research (NF-SI-0508-10335)
- Multiple Sclerosis Society
- Institut National de la Santé et de la Recherche Médicale
- Academy of Finland (129680, #213506)
- Fondazione Cariplo (2010-0728)
- Fonds Wetenschappelijk Onderzoek
- Ministero della Salute
- Kuopion Yliopistollinen Sairaala
- Oulun Yliopisto
- Regione Piemonte
- Vlaamse regering
- National Institutes of Health
- Medical Research Council
- National Institute of Neurological Disorders and Stroke (R01NS43559, R01NS043559, 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, CD6, TNFRSF1A, IRF8, single nucleotide polymorphisms, genetic association, replication, case-parent trios, disease susceptibility loci, European populations
- MeSH terms
- Interferon Regulatory Factor-8, Antigens, Differentiation, T-Lymphocyte, Humans, Multiple Sclerosis, Antigens, CD, Case-Control Studies, Polymorphism, Single Nucleotide, Receptors, Tumor Necrosis Factor, Type I, Interferon Regulatory Factors
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