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Gref, A.* ; Merid, S.K.* ; Gruzieva, O.* ; Ballereau, S.* ; Becker, A.* ; Bellander, T.* ; Bergstrom, A.* ; Bosse, Y.* ; Bottai, M.* ; Chan-Yeung, M.* ; Fuertes, E. ; Ierodiakonou, D.* ; Jiang, R.X.* ; Joly, S.* ; Jones, M.* ; Kobor, M.S.* ; Korek, M.* ; Kozyrskyj, A.L.* ; Kumar, A.* ; Lemonnier, N.* ; MacIntyre, E.A. ; Menard, C.* ; Nickle, D.C.* ; Obeidat, M.* ; Pellet, J.* ; Standl, M. ; Saaf, A.* ; Söderhäll, C.* ; Tiesler, C.M.T.* ; van den Berge, M.* ; Vonk, J.M.* ; Vora, H.* ; Xu, C.* ; Antò, J.M.* ; Auffray, C.* ; Brauer, M.* ; Bousquet, J.* ; Brunekreef, B.* ; Gauderman, W.J.* ; Heinrich, J. ; Kere, J.* ; Koppelman, G.H.* ; Postma, D.* ; Carlsten, C.* ; Pershagen, G.* ; Melén, E.*

Genome-wide interaction analysis of air pollution exposure and childhood asthma with functional follow-up.

Am. J. Respir. Crit. Care Med. 195, 1373-1383 (2017)
Publ. Version/Full Text Research data DOI
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Genome-wide Interaction Study ; Methylation ; Gene Expression ; Expression Quantitative Trait Locus ; Children; Land-use Regression; Obstructive Pulmonary-disease; Gene-environment Interaction; Tobacco-smoke Exposure; Lung-function; Escape Project; Birth Cohort; Association Scans; Diesel Exhaust; Large-scale
ISSN (print) / ISBN 1073-449X
e-ISSN 1535-4970
Quellenangaben Volume: 195, Issue: 10, Pages: 1373-1383 Article Number: , Supplement: ,
Publisher American Thoracic Society
Publishing Place New York
Reviewing status Peer reviewed