Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 195, Issue 10, Pages 1373-1383Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.201605-1026OC
Keywords
genome-wide interaction study; methylation; gene expression; expression quantitative trait locus; children
Categories
Funding
- Swedish Research Council
- Swedish Heart-Lung Foundation
- Freemason Child House Foundation in Stockholm
- Centre for Allergy Research
- Stockholm County Council (ALF)
- Strategic Research Program (SFO) in Epidemiology at Karolinska Institutet
- MeDALL (Mechanisms of the Development of Allergy) a collaborative project conducted within the European Union [261357]
- Swedish Foundation for Strategic Research [SSF RBc08-0027]
- Swedish Research Council Formas
- Swedish Environment Protection Agency
- Munich Center of Health Sciences (MCHEALTH) as part of the Ludwig-Maximilians University Munich LMU innovative
- Dutch Asthma Foundation [3.4.01.26, 3.2.06.022, 3.4.09.081, 3.2.10.085CO]
- ZON-MW Netherlands Organization for Health Research and Development [912-03-031]
- Stichting Astmabestrijding
- Ministry of the Environment
- European Commission [018996, LSH-2004-1.2.5-1]
- National Institute of Environmental Health Sciences [011627, 07048, 022719]
- NHLBI [087680]
- Canadian Institutes of Health Research
- British Columbia Lung Association
- Manitoba Medical Service Foundation
- Chaire de pneumologie de la Fondation JD Begin de l'Universite Laval
- Fondation de l'Institut universitaire de cardiologie et de pneumologie de Quebec
- Respiratory Health Network of the FRQS
- Canadian Institutes of Health Research [MOP-123369]
- Cancer Research Society
- Read for the Cure
- Fonds de recherche Quebec - Sante (FRQS)
- [264357]
Ask authors/readers for more resources
Rationale: The evidence supporting an association between traffic related air pollution exposure and incident childhood asthma is inconsistent and may depend on genetic factors. Objectives: To identify gene-environment interaction effects on childhood asthma using genome-wide single-nucleotide polymorphism (SNP) data and air pollution exposure. Identified loci were further analyzed at epigenetic and transcriptomic levels. Methods: We used land use regression models to estimate individual air pollution exposure (represented by outdoor NO2 levels) at the birth address and performed a genome-wide interaction study for doctors' diagnoses of asthma up to 8 years in three European birth cohorts (n = 1,534) with look-up for interaction in two separate North American cohorts, CHS (Children's Health Study) and CAPPS/SAGE (Canadian Asthma Primary Prevention Study/Study of Asthma, Genetics and Environment) (n = 1,602 and 186 subjects, respectively). We assessed expression quantitative trait locus effects in human lung specimens and blood, as well as associations among, air pollution exposure, methylation, and transcriptomic patterns. Measurements and Main Results: In the European cohorts, 186 SNPs had an interaction P < 1 x 10(-4) and a look-up evaluation of these disclosed 8 SNPs in 4 loci, with an interaction P < 0.05 in the large CHS study, but not in CAPPS/SAGE. Three SNPs within adenylate cyclase 2 (ADCY2) showed the same direction of the interaction effect and were found to influence ADCY2 gene expression in peripheral blood (P = 4.50 x 10(-4)). One other SNP with P < 0.05 for interaction in CHS, rs686237, strongly influenced UDP-Gal:betaGlcNAc beta-1,4-galactosyltransferase, polypeptide 5 (B4GALT5) expression in lung tissue (P =1.18 x 10(-17)). Air pollution exposure was associated with differential discs, large homolog 2 (DLG2) methylation and expression. Conclusions: Our results indicated that gene-environment interactions are important for asthma development and provided supportive evidence for interaction with air pollution for ADCY2, B4GALT5, and DLG2.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available