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The Genetic Association of Variants in CD6, TNFRSF1A and IRF8 to Multiple Sclerosis: A Multicenter Case-Control Study
- Source :
- Leppa, V, Surakka, I, Tienari, P J, Elovaara, I, Compston, A, Sawcer, S, Robertson, N, de Jager, P L, Aubin, C, Hafler, D A, Bang Oturai, A, Bach Søndergaard, H, Sellebjerg, F, Sørensen, P S, Hemmer, B, Cepok, S, Winkelmann, J, Wichmann, H-E, Bustamente, M F, Montalban, X, Olsson, T, Kockum, I, Hillert, J, Alfredsson, L, Goris, A, Dubois, B, Mero, I-L, Smestad, C, Celius, E G, Harbo, H F, D'Alfonso, S, Bergamaschi, L, Leone, M, Ristori, G, Kappos, L, Hauser, D L, Cornu-Rebeix, I, Fontaine, B, Boonen, S, Polman, C H, Palotie, A, Peltonen, L & Saarela, J 2011, ' The Genetic Association of Variants in CD6, TNFRSF1A and IRF8 to Multiple Sclerosis: A Multicenter Case-Control Study ', PLoS ONE, vol. 6, no. 4, e18813 . https://doi.org/10.1371/journal.pone.0018813, PLoS, PLoS ONE, 6(4):e18813. Public Library of Science, PLoS ONE, Vol 6, Iss 4, p e18813 (2011), PLoS ONE, PLoS ONE 6:e18813 (2011)
- Publication Year :
- 2011
-
Abstract
- 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.<br />United States. National Institutes of Health (grant RO1 NS 43559)<br />United States. National Institutes of Health (grant RO1 NS049477)<br />Academy of Finland. Center of Excellence for Complex Disease Genetics (grant 213506)<br />Academy of Finland. Center of Excellence for Complex Disease Genetics (grant 129680)<br />Sigrid Jusélius stiftelse<br />Biocentrum Helsinki Foundation<br />Helsinki University. Central Hospital Research Foundation<br />Neuropromise EU project (grant LSHM-CT-2005-018637)<br />Wellcome Trust (London, England) (grant 089061/Z/09/Z)<br />Cambridge NIHR Biomedical Research Centre<br />The Danish Council for Strategic Research (grant 2142-08-0039)<br />Italian Foundation for Multiple Sclerosis (FISM grants 2008/R/11)<br />Regione Piemonte Ricerca Sanitaria Finalizzata (2007, 2008)<br />Fondazione Cariplo (grant n° 2010- 0728)<br />Italian Ministry of Health<br />CRT Foundation<br />National Multiple Sclerosis Society (U.S.)<br />Swiss Multiple Sclerosis Society<br />United States. National Institutes of Health (R01 NS067305)
- Subjects :
- Antigens, Differentiation, T-Lymphocyte
Multiple Sclerosis
Clinical Research Design
Immunology
lcsh:Medicine
Autoimmunity
Single-nucleotide polymorphism
Genome-wide association study
Biology
Polymorphism, Single Nucleotide
Autoimmune Diseases
Pathogenesis
03 medical and health sciences
0302 clinical medicine
Antigens, CD
Genetics
medicine
Humans
SNP
lcsh:Science
Genetic Association Studies
030304 developmental biology
Genetic association
0303 health sciences
Multidisciplinary
Multiple sclerosis
lcsh:R
Case-control study
Human Genetics
medicine.disease
Demyelinating Disorders
R1
3. Good health
Neurology
Receptors, Tumor Necrosis Factor, Type I
Case-Control Studies
Genetics of Disease
Interferon Regulatory Factors
Etiology
Medicine
Clinical Immunology
lcsh:Q
Meta-Analyses
030217 neurology & neurosurgery
Research Article
Subjects
Details
- ISSN :
- 20050186 and 19326203
- Database :
- OpenAIRE
- Journal :
- Leppa, V, Surakka, I, Tienari, P J, Elovaara, I, Compston, A, Sawcer, S, Robertson, N, de Jager, P L, Aubin, C, Hafler, D A, Bang Oturai, A, Bach Søndergaard, H, Sellebjerg, F, Sørensen, P S, Hemmer, B, Cepok, S, Winkelmann, J, Wichmann, H-E, Bustamente, M F, Montalban, X, Olsson, T, Kockum, I, Hillert, J, Alfredsson, L, Goris, A, Dubois, B, Mero, I-L, Smestad, C, Celius, E G, Harbo, H F, D'Alfonso, S, Bergamaschi, L, Leone, M, Ristori, G, Kappos, L, Hauser, D L, Cornu-Rebeix, I, Fontaine, B, Boonen, S, Polman, C H, Palotie, A, Peltonen, L & Saarela, J 2011, ' The Genetic Association of Variants in CD6, TNFRSF1A and IRF8 to Multiple Sclerosis: A Multicenter Case-Control Study ', PLoS ONE, vol. 6, no. 4, e18813 . https://doi.org/10.1371/journal.pone.0018813, PLoS, PLoS ONE, 6(4):e18813. Public Library of Science, PLoS ONE, Vol 6, Iss 4, p e18813 (2011), PLoS ONE, PLoS ONE 6:e18813 (2011)
- Accession number :
- edsair.doi.dedup.....336591664e0acd7a628309e927acab61