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@article{Gref:2017:10.1164/rccm.201605-1026OC,
author = {Gref, A and Merid, SK and Gruzieva, O and Ballereau, S and Becker, A and Bellander, T and Bergstrom, A and Bosse, Y and Bottai, M and Chan-Yeung, M and Fuertes, E and Ierodiakonou, D and Jiang, R and Joly, S and Jones, M and Kobor, MS and Korek, M and Kozyrskyj, AL and Kumar, A and Lemonnier, N and MacIntyre, E and Menard, C and Nickle, D and Obeidat, M and Pellet, J and Standl, M and Saaf, A and Soderhall, C and Tiesler, CMT and van, den Berge M and Vonk, JM and Vora, H and Xu, C-J and Anto, JM and Auffray, C and Brauer, M and Bousquet, J and Brunekreef, B and Gauderman, WJ and Heinrich, J and Kere, J and Koppelman, GH and Postma, D and Carlsten, C and Pershagen, G and Melen, E},
doi = {10.1164/rccm.201605-1026OC},
journal = {AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE},
pages = {1373--1383},
title = {Genome-Wide Interaction Analysis of Air Pollution Exposure and Childhood Asthma with Functional Follow-up},
url = {http://dx.doi.org/10.1164/rccm.201605-1026OC},
volume = {195},
year = {2017}
}

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TY  - JOUR
AB  - 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 × 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 associ
AU  - Gref,A
AU  - Merid,SK
AU  - Gruzieva,O
AU  - Ballereau,S
AU  - Becker,A
AU  - Bellander,T
AU  - Bergstrom,A
AU  - Bosse,Y
AU  - Bottai,M
AU  - Chan-Yeung,M
AU  - Fuertes,E
AU  - Ierodiakonou,D
AU  - Jiang,R
AU  - Joly,S
AU  - Jones,M
AU  - Kobor,MS
AU  - Korek,M
AU  - Kozyrskyj,AL
AU  - Kumar,A
AU  - Lemonnier,N
AU  - MacIntyre,E
AU  - Menard,C
AU  - Nickle,D
AU  - Obeidat,M
AU  - Pellet,J
AU  - Standl,M
AU  - Saaf,A
AU  - Soderhall,C
AU  - Tiesler,CMT
AU  - van,den Berge M
AU  - Vonk,JM
AU  - Vora,H
AU  - Xu,C-J
AU  - Anto,JM
AU  - Auffray,C
AU  - Brauer,M
AU  - Bousquet,J
AU  - Brunekreef,B
AU  - Gauderman,WJ
AU  - Heinrich,J
AU  - Kere,J
AU  - Koppelman,GH
AU  - Postma,D
AU  - Carlsten,C
AU  - Pershagen,G
AU  - Melen,E
DO  - 10.1164/rccm.201605-1026OC
EP  - 1383
PY  - 2017///
SN  - 1073-449X
SP  - 1373
TI  - Genome-Wide Interaction Analysis of Air Pollution Exposure and Childhood Asthma with Functional Follow-up
T2  - AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
UR  - http://dx.doi.org/10.1164/rccm.201605-1026OC
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000401501400016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/59797
VL  - 195
ER  -

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