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dc.contributor.authorLenz, TLen_US
dc.contributor.authorDeutsch, AJen_US
dc.contributor.authorHan, Ben_US
dc.contributor.authorHu, Xen_US
dc.contributor.authorOkada, Yen_US
dc.contributor.authorEyre, Sen_US
dc.contributor.authorKnapp, Men_US
dc.contributor.authorZhernakova, Aen_US
dc.contributor.authorHuizinga, TWJen_US
dc.contributor.authorAbecasis, Gen_US
dc.contributor.authorBecker, Jen_US
dc.contributor.authorBoeckxstaens, GEen_US
dc.contributor.authorChen, WMen_US
dc.contributor.authorFranke, Aen_US
dc.contributor.authorGladman, DDen_US
dc.contributor.authorGockel, Ien_US
dc.contributor.authorGutierrez-Achury, Jen_US
dc.contributor.authorMartin, Jen_US
dc.contributor.authorNair, RPen_US
dc.contributor.authorNöthen, MMen_US
dc.contributor.authorOnengut-Gumuscu, Sen_US
dc.contributor.authorRahman, Pen_US
dc.contributor.authorRantapää-Dahlqvist, Sen_US
dc.contributor.authorStuart, PEen_US
dc.contributor.authorTsoi, LCen_US
dc.contributor.authorVan Heel, DAen_US
dc.contributor.authorWorthington, Jen_US
dc.contributor.authorWouters, MMen_US
dc.contributor.authorKlareskog, Len_US
dc.contributor.authorElder, JTen_US
dc.contributor.authorGregersen, PKen_US
dc.contributor.authorSchumacher, Jen_US
dc.contributor.authorRich, SSen_US
dc.contributor.authorWijmenga, Cen_US
dc.contributor.authorSunyaev, SRen_US
dc.contributor.authorDe Bakker, PIWen_US
dc.contributor.authorRaychaudhuri, Sen_US
dc.date.accessioned2016-04-21T12:56:09Z
dc.date.issued2015-08-27en_US
dc.identifier.issn1061-4036en_US
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/11945
dc.descriptionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552599/en_US
dc.description.abstract© 2015 Nature America, Inc. All rights reserved. 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 (ncases = 5,337), type 1 diabetes (T1D; ncases = 5,567), psoriasis vulgaris (ncases = 3,089), idiopathic achalasia (ncases = 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 × 10-12; T1D, P = 2.4 × 10-10; psoriasis, P = 5.9 × 10-6; celiac disease, P = 1.2 × 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 × 10-3; T1D, P = 8.6 × 10-27; celiac disease, P = 6.0 × 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.en_US
dc.format.extent1085 - 1090en_US
dc.language.isoenen_US
dc.relation.ispartofNature Geneticsen_US
dc.relation.urihttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552599/
dc.titleWidespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseasesen_US
dc.typeArticle
dc.identifier.doi10.1038/ng.3379en_US
pubs.issue9en_US
pubs.notesNot knownen_US
pubs.publication-statusPublisheden_US
pubs.volume47en_US


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