title: Gene-environment interaction for childhood asthma and exposure to farming in Central Europe.
abstract: BACKGROUND
  Asthma is a disease in which both genetic and environmental factors play important roles. The farming environment has consistently been associated with protection from childhood asthma and atopy, and interactions have been reported with polymorphisms in innate immunity genes.
  
  
  OBJECTIVE
  To detect gene-environment interactions for asthma and atopy in the farming environment.
  
  
  METHODS
  We performed a genome-wide interaction analysis for asthma and atopy by using 500,000 genotyped single nucleotide polymorphisms (SNPs) and farm-related exposures in 1708 children from 4 rural regions of Central Europe. We also tested selectively for interactions between farm exposures and 7 SNPs that emerged as genome-wide significant in a large meta-analysis of childhood asthma and 5 SNPs that had been reported previously as interacting with farm exposures for asthma or atopy.
  
  
  RESULTS
  Neither the asthma-associated SNPs nor the SNPs previously published for interactions with asthma showed significant interactions. The genome-wide interaction study did not reveal any significant interactions with SNPs within genes in the range of interacting allele frequencies from 30% to 70%, for which our study was well powered. Among rarer SNPs, we identified 15 genes with strong interactions for asthma or atopy in relation to farming, contact with cows and straw, or consumption of raw farm milk.
  
  
  CONCLUSIONS
  Common genetic polymorphisms are unlikely to moderate the protective influence of the farming environment on childhood asthma and atopy, but rarer variants, particularly of the glutamate receptor, metabotropic 1 gene, may do so. Given the limited statistical power of our study, these findings should be interpreted with caution before being replicated in independent farm populations.
authors.affiliation: University Children's Hospital Munich, Munich, Germany. markus.ege@med.uni-muenchen.de
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Ege
authors.forename: David P
authors.initials: DP
authors.lastname: Strachan
authors.forename: William O C M
authors.initials: WO
authors.lastname: Cookson
authors.forename: Miriam F
authors.initials: MF
authors.lastname: Moffatt
authors.forename: Ivo
authors.initials: I
authors.lastname: Gut
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Michael
authors.initials: M
authors.lastname: Kabesch
authors.forename: Jon
authors.initials: J
authors.lastname: Genuneit
authors.forename: Gisela
authors.initials: G
authors.lastname: Büchele
authors.forename: Barbara
authors.initials: B
authors.lastname: Sozanska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Boznanski
authors.forename: Paul
authors.initials: P
authors.lastname: Cullinan
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Horak
authors.forename: Christian
authors.initials: C
authors.lastname: Bieli
authors.forename: Charlotte
authors.initials: C
authors.lastname: Braun-Fahrländer
authors.forename: Dick
authors.initials: D
authors.lastname: Heederik
authors.forename: Erika
authors.initials: E
authors.lastname: von Mutius
mesh_terms: D000293:Adolescent; D000383:Agriculture; D001249:Asthma / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D004781:Environmental Exposure / Q000009:adverse effects*; D005060:Europe; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D012424:Rural Population
chemical_list: D007073:Immunoglobulin E