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Baurecht, H.* ; Hotze, M.* ; Brand, S.* ; Büning, C.* ; Cormican, P.* ; Corvin, A.* ; Ellinghaus, D.* ; Ellinghaus, E.* ; Esparza-Gordillo, J.* ; Fölster-Holst, R.* ; Franke, A.* ; Gieger, C. ; Hubner, N.* ; Illig, T. ; Irvine, A.D.* ; Kabesch, M.* ; Lee, Y.A.* ; Lieb, W.* ; Marenholz, I.* ; McLean, W.H.* ; Morris, D.W.* ; Mrowietz, U.* ; Nair, R.P.* ; Nöthen, M.M.* ; Novak, N.* ; O'Regan, G.M.* ; Schreiber, S.* ; Smith, C.* ; Strauch, K. ; Stuart, P.E.* ; Trembath, R.* ; Tsoi, L.C.* ; Weichenthal, M.* ; Barker, J.* ; Elder, J.T.* ; Weidinger, S.* ; Cordell, H.J.* ; Brown, S.J.*

Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms.

Am. J. Hum. Genet. 96, 104-120 (2015)
Verlagsversion DOI PMC
Closed
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Atopic 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Classical Hla Alleles; Analysis Identifies 3; Of-function Variants; Cd8(+) T-cells; Susceptibility Loci; Cellular Activator; Ifn-gamma; Association; Population; Filaggrin
Sprache englisch
Veröffentlichungsjahr 2015
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 0002-9297
e-ISSN 1537-6605
Zeitschrift American Journal of Human Genetics, The
Quellenangaben Band: 96, Heft: 1, Seiten: 104-120 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort New York, NY
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Institute of Genetic Epidemiology (IGE)
POF Topic(s) 30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504091-004
G-504100-001
PubMed ID 25574825
DOI 10.1016/j.ajhg.2014.12.004
WOS ID WOS:000347707800008
Scopus ID 84920747894
Erfassungsdatum 2015-01-14
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