title: The eczema risk variant on chromosome 11q13 (rs7927894) in the population-based ALSPAC cohort: a novel susceptibility factor for asthma and hay fever.
abstract: 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 9300 individuals of the prospectively evaluated Avon Longitudinal Study of Parents and Children 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 phenotype atopic asthma plus eczema [odds ratio (OR) = 1.50; 95% confidence interval (CI) 1.20-1.88; P = 3.7 × 10(-4)] and hay fever plus eczema (OR = 1.37; 95% CI 1.15-1.62; P = 3.8 × 10(-4)). We replicated the effects of rs7927894[T] on eczema-associated asthma and hay fever independently in the German GENUFAD (GEnetic studies in NUclear Families with Atopic Dermatitis) study and show that they are significantly larger than the effect observed in eczema. The estimated population attributable risk fractions for eczema, 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 Multicenter Allergy Study 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.
authors.affiliation: Pediatric Pneumology and Immunology, Charite´-University Medicine Berlin, 13353 Berlin, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Marenholz
authors.forename: Anja
authors.initials: A
authors.lastname: Bauerfeind
authors.forename: Jorge
authors.initials: J
authors.lastname: Esparza-Gordillo
authors.forename: Tamara
authors.initials: T
authors.lastname: Kerscher
authors.forename: Raquel
authors.initials: R
authors.lastname: Granell
authors.forename: Renate
authors.initials: R
authors.lastname: Nickel
authors.forename: Susanne
authors.initials: S
authors.lastname: Lau
authors.forename: John
authors.initials: J
authors.lastname: Henderson
authors.forename: Young-Ae
authors.initials: YA
authors.lastname: Lee
mesh_terms: D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D015331:Cohort Studies; D004485:Eczema / Q000235:genetics*; D000091344:Filaggrin Proteins; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics; D016013:Likelihood Functions; D016015:Logistic Models; D008137:Longitudinal Studies; D015233:Models, Statistical; D009154:Mutation / Q000235:genetics; D016017:Odds Ratio; D012307:Risk Factors; D006113:United Kingdom
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins