title: Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis.
abstract: Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10(-9)), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10(-8)). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis.
authors.affiliation: Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.
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mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5; D016207:Cytokines / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000276:immunology; D004817:Epidermis / Q000276:immunology; D005260:Female; D000091344:Filaggrin Proteins; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics; D016547:Kinesins / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D014157:Transcription Factors / Q000235:genetics
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; C087415:KIF3A protein, human; C490319:OVOL1 protein, human; D014157:Transcription Factors; D016547:Kinesins