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Lookup NU author(s): Professor Heather Cordell
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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.
Author(s): Baurecht H, Hotze M, Brand S, Buning C, Cormican P, Corvin A, Ellinghaus D, Ellinghaus E, Esparza-Gordillo J, Folster-Holst R, Franke A, Gieger C, Hubner N, Illig T, Irvine AD, Kabesch M, Lee YAE, Lieb W, Marenholz I, McLean WHI, Morris DW, Mrowietz U, Nair R, Nothen MM, Novak N, O'Regan GM, Schreiber S, Smith C, Strauch K, Stuart PE, Trembath R, Tsoi LC, Weichenthal M, Barker J, Elder JT, Weidinger S, Cordell HJ, Brown SJ, PAGE Consortium
Publication type: Article
Publication status: Published
Journal: American Journal of Human Genetics
Year: 2015
Volume: 96
Issue: 1
Pages: 104-120
Print publication date: 08/01/2015
Online publication date: 08/01/2015
Acceptance date: 05/12/2014
Date deposited: 07/04/2015
ISSN (print): 0002-9297
ISSN (electronic): 1537-6605
Publisher: Cell Press
URL: http://dx.doi.org/10.1016/j.ajhg.2014.12.004
DOI: 10.1016/j.ajhg.2014.12.004
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