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Weidinger, S.* ; Willis-Owen, S.A.* ; Kamatani, Y.* ; Baurecht, H.* ; Morar, N.* ; Liang, L.* ; Edser, P.* ; Street, T.* ; Rodriguez, E.* ; O'Regan, G.M.* ; Beattie, P.* ; Fölster-Holst, R.* ; Franke, A.* ; Novak, N.* ; Fahy, C.M.* ; Winge, M.C.G.* ; Kabesch, M.* ; Illig, T. ; Heath, S.* ; Söderhäll, C.* ; Melén, E.* ; Pershagen, G.* ; Kere, J.* ; Bradley, M.* ; Liedén, A.* ; Nordenskjöld, M.* ; Harper, J.I.* ; McLean, W.H.* ; Brown, S.J.* ; Cookson, W.O.* ; Lathrop, G.M.* ; Irvine, A.D.* ; Moffatt, M.F.*

A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis.

Hum. Mol. Genet. 22, 4841-4856 (2013)
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Atopic dermatitis (AD) is the most common dermatological disease of childhood. Many children with AD have asthma and AD shares regions of genetic linkage with psoriasis, another chronic inflammatory skin disease. We present here a genome-wide association study (GWAS) of childhood-onset AD in 1563 European cases with known asthma status and 4054 European controls. Using Illumina genotyping followed by imputation, we generated 268 034 consensus genotypes and in excess of 2 million single nucleotide polymorphisms (SNPs) for analysis. Association signals were assessed for replication in a second panel of 2286 European cases and 3160 European controls. Four loci achieved genome-wide significance for AD and replicated consistently across all cohorts. These included the epidermal differentiation complex (EDC) on chromosome 1, the genomic region proximal to LRRC32 on chromosome 11, the RAD50/IL13 locus on chromosome 5 and the major histocompatibility complex (MHC) on chromosome 6; reflecting action of classical HLA alleles. We observed variation in the contribution towards co-morbid asthma for these regions of association. We further explored the genetic relationship between AD, asthma and psoriasis by examining previously identified susceptibility SNPs for these diseases. We found considerable overlap between AD and psoriasis together with variable coincidence between allergic rhinitis (AR) and asthma. Our results indicate that the pathogenesis of AD incorporates immune and epidermal barrier defects with combinations of specific and overlapping effects at individual loci.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Classical Hla Alleles ; Susceptibility Loci ; Japanese Population ; Filaggrin Mutations ; Reveals Association ; Extended Haplotype ; Genetic-variation ; Common Variants ; Birth Cohort ; Large-scale
Language english
Publication Year 2013
HGF-reported in Year 2013
ISSN (print) / ISBN 0964-6906
e-ISSN 1460-2083
Journal Human Molecular Genetics
Quellenangaben Volume: 22, Issue: 23, Pages: 4841-4856 Article Number: , Supplement: ,
Publisher Oxford University Press
Reviewing status Peer reviewed
Institute(s) Research Unit Molecular Epidemiology (AME)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504200-001
PubMed ID 23886662
DOI 10.1093/hmg/ddt317
WOS ID WOS:000326973000016
Scopus ID 84887517673
Erfassungsdatum 2013-11-27
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