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

Gref, Anna and Merid, Simon K. and Gruzieva, Olena and Ballereau, Stéphane and Becker, Allan and Bellander, Tom and Bergström, Anna and Bossé, Yohan and Bottai, Matteo and Chan-Yeung, Moira and Fuertes, Elaine and Ierodiakonou, Despo and Jiang, Ruiwei and Joly, Stéphane and Jones, Meaghan and Kobor, Michael S. and Korek, Michal and Kozyrskyj, Anita L. and Kumar, Ashish and Lemonnier, Nathanaël and MacIntyre, Elaina and Ménard, Camille and Nickle, David and Obeidat, Ma'en and Pellet, Johann and Standl, Marie and Sääf, Annika and Söderhäll, Cilla and Tiesler, Carla M. T. and van den Berge, Maarten and Vonk, Judith M. and Vora, Hita and Xu, Cheng-Jian and Antó, Josep M. and Auffray, Charles and Brauer, Michael and Bousquet, Jean and Brunekreef, Bert and Gauderman, W. James and Heinrich, Joachim and Kere, Juha and Koppelman, Gerard H. and Postma, Dirkje and Carlsten, Christopher and Pershagen, Göran and Melén, Erik. (2017) Genome-wide interaction analysis of air pollution exposure and childhood asthma with functional follow-up. American journal of respiratory and critical care medicine, 195 (10). pp. 1373-1383.

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Official URL: http://edoc.unibas.ch/55414/

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Abstract

The evidence supporting an association between traffic-related air pollution exposure and incident childhood asthma is inconsistent and may depend on genetic factors.; 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.; 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.; 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.; 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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Exposome Science (Probst-Hensch)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Exposome Science (Probst-Hensch)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Kumar, Ashish
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Thoracic Society
ISSN:0003-0805
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:14 Jun 2017 14:22
Deposited On:14 Jun 2017 14:22

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