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- Title
Genome-Wide Interaction Analysis of Air Pollution Exposure and Childhood Asthma with Functional Follow-up.
- Authors
Gref, Anna; Merid, Simon K.; Gruzieva, Olena; Ballereau, Stéphane; Becker, Allan; Bellander, Tom; Bergström, Anna; Bossé, Yohan; Bottai, Matteo; Moira Chan-Yeung; Fuertes, Elaine; Ierodiakonou, Despo; Ruiwei Jiang; Joly, Stéphane; Jones, Meaghan; Kobor, Michael S.; Korek, Michal; Kozyrskyj, Anita L.; Kumar, Ashish; Lemonnier, Nathanaël
- Abstract
<bold>Rationale: </bold>The evidence supporting an association between traffic-related air pollution exposure and incident childhood asthma is inconsistent and may depend on genetic factors.<bold>Objectives: </bold>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.<bold>Methods: </bold>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.<bold>Measurements and Main Results: </bold>In the European cohorts, 186 SNPs had an interaction P < 1 × 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 × 10-4). One other SNP with P < 0.05 for interaction in CHS, rs686237, strongly influenced UDP-Gal:betaGlcNAc β-1,4-galactosyltransferase, polypeptide 5 (B4GALT5) expression in lung tissue (P = 1.18 × 10-17). Air pollution exposure was associated with differential discs, large homolog 2 (DLG2) methylation and expression.<bold>Conclusions: </bold>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.
- Subjects
EUROPE; NORTH America; AIR pollution; ASTHMA; GENETIC polymorphisms; LONGITUDINAL method; RESEARCH funding; PHENOTYPES
- Publication
American Journal of Respiratory & Critical Care Medicine, 2017, Vol 195, Issue 10, p1373
- ISSN
1073-449X
- Publication type
journal article
- DOI
10.1164/rccm.201605-1026OC