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

Authors:
Stephan Weidinger, Saffron A G Willis-Owen, Yoichiro Kamatani, Hansjörg Baurecht, Nilesh Morar, Liming Liang, Pauline Edser, Teresa Street, Elke Rodriguez, Grainne M O'Regan, Paula Beattie, Regina Fölster-Holst, Andre Franke, Natalija Novak, Caoimhe M Fahy, Mårten C G Winge, Michael Kabesch, Thomas Illig, Simon Heath, Cilla Söderhäll, Erik Melén, Göran Pershagen, Juha Kere, Maria Bradley, Agne Lieden, Magnus Nordenskjold, John I Harper, W H Irwin McLean, Sara J Brown, William O C Cookson, G Mark Lathrop, Alan D Irvine, Miriam F Moffatt
Year of publication:
2013
Volume:
22
Issue:
23
Issn:
0964-6906
Journal title abbreviated:
HUM MOL GENET
Journal title long:
Human molecular genetics
Impact factor:
5.985
Abstract:
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.