title: A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis.
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.
authors.affiliation: Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein and.
authors.forename: Stephan
authors.initials: S
authors.lastname: Weidinger
authors.forename: Saffron A G
authors.initials: SA
authors.lastname: Willis-Owen
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kamatani
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Baurecht
authors.forename: Nilesh
authors.initials: N
authors.lastname: Morar
authors.forename: Liming
authors.initials: L
authors.lastname: Liang
authors.forename: Pauline
authors.initials: P
authors.lastname: Edser
authors.forename: Teresa
authors.initials: T
authors.lastname: Street
authors.forename: Elke
authors.initials: E
authors.lastname: Rodriguez
authors.forename: Grainne M
authors.initials: GM
authors.lastname: O'Regan
authors.forename: Paula
authors.initials: P
authors.lastname: Beattie
authors.forename: Regina
authors.initials: R
authors.lastname: Fölster-Holst
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.forename: Natalija
authors.initials: N
authors.lastname: Novak
authors.forename: Caoimhe M
authors.initials: CM
authors.lastname: Fahy
authors.forename: Mårten C G
authors.initials: MC
authors.lastname: Winge
authors.forename: Michael
authors.initials: M
authors.lastname: Kabesch
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Simon
authors.initials: S
authors.lastname: Heath
authors.forename: Cilla
authors.initials: C
authors.lastname: Söderhäll
authors.forename: Erik
authors.initials: E
authors.lastname: Melén
authors.forename: Göran
authors.initials: G
authors.lastname: Pershagen
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.forename: Maria
authors.initials: M
authors.lastname: Bradley
authors.forename: Agne
authors.initials: A
authors.lastname: Lieden
authors.forename: Magnus
authors.initials: M
authors.lastname: Nordenskjold
authors.forename: John I
authors.initials: JI
authors.lastname: Harper
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Brown
authors.forename: William O C
authors.initials: WO
authors.lastname: Cookson
authors.forename: G Mark
authors.initials: GM
authors.lastname: Lathrop
authors.forename: Alan D
authors.initials: AD
authors.lastname: Irvine
authors.forename: Miriam F
authors.initials: MF
authors.lastname: Moffatt
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002878:Chromosomes, Human, Pair 1; D002880:Chromosomes, Human, Pair 11; D002895:Chromosomes, Human, Pair 5; D002896:Chromosomes, Human, Pair 6; D003876:Dermatitis, Atopic / Q000235:genetics*; D008040:Genetic Linkage; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult