Baurecht, Hansjoerg and Hotze, Melanie and Brand, Stephan and Buening, Carsten and Cormican, Paul and Corvin, Aiden and Ellinghaus, David and Ellinghaus, Eva and Esparza-Gordillo, Jorge and Foelster-Holst, Regina and Franke, Andre and Gieger, Christian and Hubner, Norbert and Illig, Thomas and Irvine, Alan D. and Kabesch, Michael and Lee, Young A. E. and Lieb, Wolfgang and Marenholz, Ingo and McLean, W. H. Irwin and Morris, Derek W. and Mrowietz, Ulrich and Nair, Rajan and Noethen, Markus M. and Novak, Natalija and O'Regan, Grainne M. and Schreiber, Stefan and Smith, Catherine and Strauch, Konstantin and Stuart, Philip E. and Trembath, Richard and Tsoi, Lam C. and Weichenthal, Michael and Barker, Jonathan and Elder, James T. and Weidinger, Stephan and Cordell, Heather J. and Brown, Sara J. (2015) Genome-wide Comparative Analysis of Atopic Dermatitis and Psoriasis Gives Insight into Opposing Genetic Mechanisms. AMERICAN JOURNAL OF HUMAN GENETICS, 96 (1). pp. 104-120. ISSN 0002-9297, 1537-6605
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CLASSICAL HLA ALLELES; ANALYSIS IDENTIFIES 3; OF-FUNCTION VARIANTS; CD8(+) T-CELLS; SUSCEPTIBILITY LOCI; CELLULAR ACTIVATOR; IFN-GAMMA; ASSOCIATION; POPULATION; FILAGGRIN; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Jul 2019 12:40 |
| Last Modified: | 25 Jul 2019 12:40 |
| URI: | https://pred.uni-regensburg.de/id/eprint/6109 |
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