Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

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

[img] PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
3MB

Item Type:Article
Title:Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms
Creators Name:Baurecht, H. and Hotze, M. and Brand, S. and Buening, C. and Cormican, P. and Corvin, A. and Ellinghaus, D. and Ellinghaus, E. and Esparza-Gordillo, J. and Foelster-Holst, R. and Franke, A. and Gieger, C. and Hubner, N. and Illig, T. and Irvine, A.D. and Kabesch, M. and Lee, Y.A.E. and Lieb, W. and Marenholz, I. and McLean, W.H.I. and Morris, D.W. and Mrowietz, U. and Nair, R. and Noethen, M.M. and Novak, N. and O'Regan, G.M. and Schreiber, S. and Smith, C. and Strauch, K. and Stuart, P.E. and Trembath, R. and Tsoi, L.C. and Weichenthal, M. and Barker, J. and Elder, J.T. and Weidinger, S. and Cordell, H.J. and Brown, S.J.
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.
Keywords:Alleles, Atopic Dermatitis, Case-Control Studies, Human Pair 1 Chromosomes, Human Pair 5 Chromosomes, Human Pair 6 Chromosomes, Cohort Studies, Comparative Genomic Hybridization, Genetic Loci, Genome-Wide Association Study, Logistic Models, Major Histocompatibility Complex, Single Nucleotide Polymorphism, Psoriasis, Quality Control, Reproducibility of Results
Source:American Journal of Human Genetics
ISSN:0002-9297
Publisher:Cell Press / Elsevier (U.S.A.)
Volume:96
Number:1
Page Range:104-120
Date:8 January 2015
Additional Information:Erratum in: Am J Hum Genet 97(6): 933.
Official Publication:https://doi.org/10.1016/j.ajhg.2014.12.004
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library