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Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases
DC Field | Value | Language |
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dc.contributor.author | Lenz, Tobias L. | - |
dc.contributor.author | Deutsch, Aaron J. | - |
dc.contributor.author | Han, Buhm | - |
dc.contributor.author | Hu, Xinli | - |
dc.contributor.author | Okada, Yukinori | - |
dc.contributor.author | Eyre, Stephen | - |
dc.contributor.author | Knapp, Michael | - |
dc.contributor.author | Zhernakova, Alexandra | - |
dc.contributor.author | Huizinga, Tom W. J. | - |
dc.contributor.author | Abecasis, Goncalo | - |
dc.contributor.author | Becker, Jessica | - |
dc.contributor.author | Boeckxstaens, Guy E. | - |
dc.contributor.author | Chen, Wei-Min | - |
dc.contributor.author | Franke, Andre | - |
dc.contributor.author | Gladman, Dafna D. | - |
dc.contributor.author | Gockel, Ines | - |
dc.contributor.author | Gutierrez-Achury, Javier | - |
dc.contributor.author | Martin, Javier | - |
dc.contributor.author | Nair, Rajan P. | - |
dc.contributor.author | Noethen, Markus M. | - |
dc.contributor.author | Onengut-Gumuscu, Suna | - |
dc.contributor.author | Rahman, Proton | - |
dc.contributor.author | Rantapaa-Dahlqvist, Solbritt | - |
dc.contributor.author | Stuart, Philip E. | - |
dc.contributor.author | Tsoi, Lam C. | - |
dc.contributor.author | van Heel, David A. | - |
dc.contributor.author | Worthington, Jane | - |
dc.contributor.author | Wouters, Mira M. | - |
dc.contributor.author | Klareskog, Lars | - |
dc.contributor.author | Elder, James T. | - |
dc.contributor.author | Gregersen, Peter K. | - |
dc.contributor.author | Schumacher, Johannes | - |
dc.contributor.author | Rich, Stephen S. | - |
dc.contributor.author | Wijmenga, Cisca | - |
dc.contributor.author | Sunyaev, Shamil R. | - |
dc.contributor.author | de Bakker, Paul I. W. | - |
dc.contributor.author | Raychaudhuri, Soumya | - |
dc.date.accessioned | 2023-04-26T05:10:02Z | - |
dc.date.available | 2023-04-26T05:10:02Z | - |
dc.date.created | 2023-04-21 | - |
dc.date.created | 2023-04-21 | - |
dc.date.issued | 2015-09 | - |
dc.identifier.citation | Nature Genetics, Vol.47, pp.1085-1090 | - |
dc.identifier.issn | 1061-4036 | - |
dc.identifier.uri | https://hdl.handle.net/10371/191589 | - |
dc.description.abstract | Human leukocyte antigen (HLA) genes confer substantial risk for autoimmune diseases on a log-additive scale. Here we speculated that differences in autoantigen-binding repertoires between a heterozygote's two expressed HLA variants might result in additional non-additive risk effects. We tested the non-additive disease contributions of classical HLA alleles in patients and matched controls for five common autoimmune diseases: rheumatoid arthritis (n(cases) = 5,337), type 1 diabetes (T1D; n(cases) = 5,567), psoriasis vulgaris (n(cases) = 3,089), idiopathic achalasia (n(cases) = 727) and celiac disease (ncases = 11,115). In four of the five diseases, we observed highly significant, non-additive dominance effects (rheumatoid arthritis, P = 2.5 x 10(-12); T1D, P = 2.4 x 10(-10); psoriasis, P = 5.9 x 10(-6); celiac disease, P = 1.2 x 10(-87)). In three of these diseases, the non-additive dominance effects were explained by interactions between specific classical HLA alleles (rheumatoid arthritis, P = 1.8 x 10(-3); T1D, P = 8.6 x 10(-27); celiac disease, P = 6.0 x 10(-100)). These interactions generally increased disease risk and explained moderate but significant fractions of phenotypic variance (rheumatoid arthritis, 1.4%; T1D, 4.0%; celiac disease, 4.1%) beyond a simple additive model. | - |
dc.language | 영어 | - |
dc.publisher | Nature Publishing Group | - |
dc.title | Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases | - |
dc.type | Article | - |
dc.identifier.doi | 10.1038/ng.3379 | - |
dc.citation.journaltitle | Nature Genetics | - |
dc.identifier.wosid | 000360394100021 | - |
dc.identifier.scopusid | 2-s2.0-84940590102 | - |
dc.citation.endpage | 1090 | - |
dc.citation.startpage | 1085 | - |
dc.citation.volume | 47 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Han, Buhm | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | MAJOR HISTOCOMPATIBILITY COMPLEX | - |
dc.subject.keywordPlus | SEROPOSITIVE RHEUMATOID-ARTHRITIS | - |
dc.subject.keywordPlus | CELIAC-DISEASE | - |
dc.subject.keywordPlus | PREFERENTIAL TRANSMISSION | - |
dc.subject.keywordPlus | HETEROZYGOTE ADVANTAGE | - |
dc.subject.keywordPlus | SHARED EPITOPE | - |
dc.subject.keywordPlus | GENETIC RISK | - |
dc.subject.keywordPlus | MHC | - |
dc.subject.keywordPlus | SUSCEPTIBILITY | - |
dc.subject.keywordPlus | ASSOCIATION | - |
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