Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis

Nat Genet. 2011 Dec 25;44(2):187-92. doi: 10.1038/ng.1017.

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.

Publication types

  • Meta-Analysis

MeSH terms

  • Cell Differentiation / genetics
  • Chromosomes, Human, Pair 11 / genetics
  • Chromosomes, Human, Pair 20 / genetics
  • Chromosomes, Human, Pair 5
  • Cytokines / genetics
  • DNA-Binding Proteins / genetics
  • Dermatitis, Atopic / genetics*
  • Dermatitis, Atopic / immunology
  • Epidermis / immunology
  • Female
  • Filaggrin Proteins
  • Genetic Loci*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Intermediate Filament Proteins / genetics
  • Kinesins / genetics
  • Male
  • Polymorphism, Single Nucleotide
  • Risk
  • Transcription Factors / genetics

Substances

  • Cytokines
  • DNA-Binding Proteins
  • FLG protein, human
  • Filaggrin Proteins
  • Intermediate Filament Proteins
  • KIF3A protein, human
  • OVOL1 protein, human
  • Transcription Factors
  • Kinesins