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.