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Widespread non-addi...
Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases
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Lenz, Tobias L. (author)
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Deutsch, Aaron J. (author)
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Han, Buhm (author)
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Hu, Xinli (author)
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Okada, Yukinori (author)
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Eyre, Stephen (author)
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Knapp, Michael (author)
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Zhernakova, Alexandra (author)
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Huizinga, Tom W. J. (author)
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Abecasis, Goncalo (author)
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Becker, Jessica (author)
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Boeckxstaens, Guy E. (author)
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Chen, Wei-Min (author)
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Franke, Andre (author)
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Gladman, Dafna D. (author)
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Gockel, Ines (author)
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Gutierrez-Achury, Javier (author)
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Martin, Javier (author)
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Nair, Rajan P. (author)
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Noethen, Markus M. (author)
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Onengut-Gumuscu, Suna (author)
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Rahman, Proton (author)
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- Rantapää-Dahlqvist, Solbritt, 1947- (author)
- Umeå universitet,Reumatologi
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Stuart, Philip E. (author)
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Tsoi, Lam C. (author)
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van Heel, David A. (author)
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Worthington, Jane (author)
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Wouters, Mira M. (author)
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- Klareskog, Lars (author)
- Karolinska Institutet
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Elder, James T. (author)
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Gregersen, Peter K. (author)
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Schumacher, Johannes (author)
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Rich, Stephen S. (author)
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Wijmenga, Cisca (author)
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Sunyaev, Shamil R. (author)
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de Bakker, Paul I. W. (author)
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Raychaudhuri, Soumya (author)
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(creator_code:org_t)
- 2015-08-10
- 2015
- English.
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In: Nature Genetics. - : Macmillan Publishers Ltd.. - 1061-4036 .- 1546-1718. ; 47:9, s. 1085-1090
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Lenz, Tobias L.
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Deutsch, Aaron J ...
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Han, Buhm
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Hu, Xinli
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Okada, Yukinori
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Eyre, Stephen
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show more...
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Knapp, Michael
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Zhernakova, Alex ...
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Huizinga, Tom W. ...
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Abecasis, Goncal ...
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Becker, Jessica
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Boeckxstaens, Gu ...
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Chen, Wei-Min
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Franke, Andre
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Gladman, Dafna D ...
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Gockel, Ines
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Gutierrez-Achury ...
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Martin, Javier
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Nair, Rajan P.
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Noethen, Markus ...
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Onengut-Gumuscu, ...
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Rahman, Proton
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Rantapää-Dahlqvi ...
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Stuart, Philip E ...
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Tsoi, Lam C.
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van Heel, David ...
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Worthington, Jan ...
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Wouters, Mira M.
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Klareskog, Lars
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Elder, James T.
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Gregersen, Peter ...
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Schumacher, Joha ...
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Rich, Stephen S.
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Wijmenga, Cisca
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Sunyaev, Shamil ...
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de Bakker, Paul ...
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Raychaudhuri, So ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Health Sciences
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and Public Health Gl ...
- Articles in the publication
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Nature Genetics
- By the university
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Umeå University
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Karolinska Institutet