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dc.contributor.authorBaurecht, Hansjörg
dc.contributor.authorHotze, Melanie
dc.contributor.authorBrand, Stephan
dc.contributor.authorBüning, Carsten
dc.contributor.authorCormican, Paul
dc.contributor.authorCorvin, Aiden
dc.contributor.authorEllinghaus, David
dc.contributor.authorEllinghaus, Eva
dc.contributor.authorEsparza-Gordillo, Jorge
dc.contributor.authorFölster-Holst, Regina
dc.contributor.authorFranke, Andre
dc.contributor.authorGieger, Christian
dc.contributor.authorHubner, Norbert
dc.contributor.authorIllig, Thomas
dc.contributor.authorIrvine, Alan D.
dc.contributor.authorKabesch, Michael
dc.contributor.authorLee, Young A.E.
dc.contributor.authorLieb, Wolfgang
dc.contributor.authorMarenholz, Ingo
dc.contributor.authorMcLean, W.H. Irwin
dc.contributor.authorMorris, Derek W.
dc.contributor.authorMrowietz, Ulrich
dc.contributor.authorNair, Rajan
dc.contributor.authorNöthen, Markus M.
dc.contributor.authorNovak, Natalija
dc.contributor.authorO’Regan, Grainne M.
dc.contributor.authorSchreiber, Stefan
dc.contributor.authorSmith, Catherine
dc.contributor.authorStrauch, Konstantin
dc.contributor.authorStuart, Philip E.
dc.contributor.authorTrembath, Richard
dc.contributor.authorTsoi, Lam C.
dc.contributor.authorWeichenthal, Michael
dc.contributor.authorBarker, Jonathan
dc.contributor.authorElder, James T.
dc.contributor.authorWeidinger, Stephan
dc.contributor.authorCordell, Heather J.
dc.contributor.authorBrown, Sara J.
dc.date.accessioned2018-09-20T16:00:41Z
dc.date.available2018-09-20T16:00:41Z
dc.date.issued2015-01-01
dc.identifier.citationBaurecht, Hansjörg; Hotze, Melanie; Brand, Stephan; Büning, Carsten; Cormican, Paul; Corvin, Aiden; Ellinghaus, David; Ellinghaus, Eva; Esparza-Gordillo, Jorge; Fölster-Holst, Regina; Franke, Andre; Gieger, Christian; Hubner, Norbert; Illig, Thomas; Irvine, Alan D. Kabesch, Michael; Lee, Young A.E.; Lieb, Wolfgang; Marenholz, Ingo; McLean, W.H. Irwin; Morris, Derek W.; Mrowietz, Ulrich; Nair, Rajan; Nöthen, Markus M.; Novak, Natalija; O’Regan, Grainne M.; Schreiber, Stefan; Smith, Catherine; Strauch, Konstantin; Stuart, Philip E.; Trembath, Richard; Tsoi, Lam C.; Weichenthal, Michael; Barker, Jonathan; Elder, James T.; Weidinger, Stephan; Cordell, Heather J.; Brown, Sara J. (2015). Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms. The American Journal of Human Genetics 96 (1), 104-120
dc.identifier.issn0002-9297
dc.identifier.urihttp://hdl.handle.net/10379/10376
dc.description.abstractAtopic dermatitis and psoriasis are the two most common immune-mediated inflammatory disorders affecting the skin. Genome-wide studies demonstrate a high degree of genetic overlap, but these diseases have mutually exclusive clinical phenotypes and opposing immune mechanisms. Despite their prevalence, atopic dermatitis and psoriasis very rarely co-occur within one individual. By utilizing genome-wide association study and ImmunoChip data from >19,000 individuals and methodologies developed from meta-analysis, we have identified opposing risk alleles at shared loci as well as independent disease-specific loci within the epidermal differentiation complex (chromosome 1q21.3), the Th2 locus control region (chromosome 5q31.1), and the major histocompatibility complex (chromosome 6p21-22). We further identified previously unreported pleiotropic alleles with opposing effects on atopic dermatitis and psoriasis risk in PRKRA and ANXA6/TNIP1. In contrast, there was no evidence for shared loci with effects operating in the same direction on both diseases. Our results show that atopic dermatitis and psoriasis have distinct genetic mechanisms with opposing effects in shared pathways influencing epidermal differentiation and immune response. The statistical analysis methods developed in the conduct of this study have produced additional insight from previously published data sets. The approach is likely to be applicable to the investigation of the genetic basis of other complex traits with overlapping and distinct clinical features.
dc.publisherElsevier BV
dc.relation.ispartofThe American Journal of Human Genetics
dc.subjectclassical hla alleles
dc.subjectanalysis identifies 3
dc.subjectof-function variants
dc.subjectcd8(+) t-cells
dc.subjectsusceptibility loci
dc.subjectcellular activator
dc.subjectifn-gamma
dc.subjectassociation
dc.subjectpopulation
dc.subjectfilaggrin
dc.titleGenome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms
dc.typeArticle
dc.identifier.doi10.1016/j.ajhg.2014.12.004
dc.local.publishedsourcehttps://doi.org/10.1016/j.ajhg.2014.12.004
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