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Gene-environment interaction for childhood asthma and exposure to farming in Central Europe


Ege, M J; Strachan, D P; Cookson, W O C M; Moffatt, M F; Gut, I; Lathrop, M; Kabesch, M; Genuneit, J; Büchele, G; Sozanska, B; Boznanski, A; Cullinan, P; Horak, E; Bieli, C; Braun-Fahrländer, C; Heederik, D; von Mutius, E (2011). Gene-environment interaction for childhood asthma and exposure to farming in Central Europe. Journal of Allergy and Clinical Immunology, 127(1):138-144.e4.

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.
CONCLUSION:

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.

Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

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.
CONCLUSION:

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.

Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2011
Deposited On:25 Jan 2012 21:50
Last Modified:07 Dec 2017 11:26
Publisher:Elsevier
ISSN:0091-6749
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.jaci.2010.09.041
PubMed ID:21211648

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