TY - JOUR
T1 - Genome-wide interaction analysis of air pollution exposure and childhood asthma with functional follow-up
AU - Gref, Anna
AU - Merid, Simon K.
AU - Gruzieva, Olena
AU - Ballereau, Stéphane
AU - Becker, Allan
AU - Bellander, Tom
AU - Bergström, Anna
AU - Bossé, Yohan
AU - Bottai, Matteo
AU - Chan-Yeung, Moira
AU - Fuertes, Elaine
AU - Ierodiakonou, Despo
AU - Jiang, Ruiwei
AU - Joly, Stéphane
AU - Jones, Meaghan
AU - Kobor, Michael S.
AU - Korek, Michal
AU - Kozyrskyj, Anita L.
AU - Kumar, Ashish
AU - Lemonnier, Nathanaël
AU - MacIntyre, Elaina
AU - Ménard, Camille
AU - Nickle, David
AU - Obeidat, Ma'en
AU - Pellet, Johann
AU - Standl, Marie
AU - Sääf, Annika
AU - Söderhäll, Cilla
AU - Tiesler, Carla M.T.
AU - Van Den Berge, Maarten
AU - Vonk, Judith M.
AU - Vora, Hita
AU - Xu, Cheng Jian
AU - Antó, Josep M.
AU - Auffray, Charles
AU - Brauer, Michael
AU - Bousquet, Jean
AU - Brunekreef, Bert
AU - Gauderman, W. James
AU - Heinrich, Joachim
AU - Kere, Juha
AU - Koppelman, Gerard H.
AU - Postma, Dirkje
AU - Carlsten, Christopher
AU - Pershagen, Göran
AU - Melén, Erik
N1 - Publisher Copyright:
Copyright © 2017 by the American Thoracic Society.
PY - 2017/5/15
Y1 - 2017/5/15
N2 - 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 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.
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 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.
KW - Children
KW - Expression quantitative trait locus
KW - Gene expression
KW - Genome-wide interaction study
KW - Methylation
UR - https://www.scopus.com/pages/publications/85019879967
U2 - 10.1164/rccm.201605-1026OC
DO - 10.1164/rccm.201605-1026OC
M3 - Article
C2 - 27901618
AN - SCOPUS:85019879967
SN - 1073-449X
VL - 195
SP - 1373
EP - 1383
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 10
ER -
