The eczema risk variant on chromosome 11q13 (rs7927894) in the population-based ALSPAC cohort: a novel susceptibility factor for asthma and hay fever


  • I. Marenholz
  • A. Bauerfeind
  • J. Esparza-Gordillo
  • T. Kerscher
  • R. Granell
  • R. Nickel
  • S. Lau
  • J. Henderson
  • Y.A. Lee


  • Human Molecular Genetics


  • Hum Mol Genet 20 (12): 2443-2449


  • In a genome-wide association study, a common variant on chromosome 11q13.5 (rs7927894[T]) has been identified as a susceptibility locus for eczema. We aimed to analyze the effect of this risk variant on asthma and hay fever, and to determine its impact on the general population level in over 9,300 individuals of the prospectively evaluated ALSPAC birth cohort. We demonstrate an association of rs7927894[T] with atopic asthma and with hay fever. The largest effect sizes were found in patients with the combined phenotypes atopic asthma plus eczema (OR = 1.50; 95% CI 1.20-1.88; P = 3.7x10(-4)) and hay fever plus eczema (OR = 1.37; 95% CI 1.15-1.62; P = 3.8x10(-4)). We replicated the effects of rs7927894[T] on eczema-associated asthma and hay fever independently in the German GENUFAD study, and show that they are significantly larger than the effect observed in eczema. The estimated population attributable risk fractions for eczema, associated atopic asthma, or hay fever were 9.3%, 24.9%, and 23.5%, respectively. Finally in eczema, we found a synergistic interaction of rs7927894[T] with filaggrin gene (FLG) mutations, which are a major cause of epidermal barrier dysfunction, and replicated the interaction in the German MAS birth cohort. The synergistic effect of rs7927894[T] and FLG mutations on eczema risk, as well as the association of both variants with eczema-associated atopic asthma and hay fever point to an involvement of rs7927894[T] in a functional pathway that is linked to the barrier defect.