Dataset Information

Genome-Wide Interaction Analysis of Air Pollution Exposure and Childhood Asthma with Functional Follow-up.

ABSTRACT:

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.

SUBMITTER: Gref A

PROVIDER: S-EPMC5443897 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Publications

Genome-Wide Interaction Analysis of Air Pollution Exposure and Childhood Asthma with Functional Follow-up.

Gref Anna A Merid Simon K SK Gruzieva Olena O Ballereau Stéphane S Becker Allan A Bellander Tom T Bergström Anna A Bossé Yohan Y Bottai Matteo M Chan-Yeung Moira M Fuertes Elaine E Ierodiakonou Despo D Jiang Ruiwei R Joly Stéphane S Jones Meaghan M Kobor Michael S MS Korek Michal M Kozyrskyj Anita L AL Kumar Ashish A Lemonnier Nathanaël N MacIntyre Elaina E Ménard Camille C Nickle David D Obeidat Ma'en M Pellet Johann J Standl Marie M Sääf Annika A Söderhäll Cilla C Tiesler Carla M T CMT van den Berge Maarten M Vonk Judith M JM Vora Hita H Xu Cheng-Jian CJ Antó Josep M JM Auffray Charles C Brauer Michael M Bousquet Jean J Brunekreef Bert B Gauderman W James WJ Heinrich Joachim J Kere Juha J Koppelman Gerard H GH Postma Dirkje D Carlsten Christopher C Pershagen Göran G Melén Erik E

American journal of respiratory and critical care medicine 20170501 10

<h4>Rationale</h4>The evidence supporting an association between traffic-related air pollution exposure and incident childhood asthma is inconsistent and may depend on genetic factors.<h4>Objectives</h4>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.<h4>Methods</h4>We used land use regression models to estimate ...[more]

PMID: 27901618

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Project description:ImportanceExposure to outdoor air pollution contributes to childhood asthma development, but many studies lack the geographic, racial and ethnic, and socioeconomic diversity to evaluate susceptibility by individual-level and community-level contextual factors.ObjectiveTo examine early life exposure to fine particulate matter (PM2.5) and nitrogen oxide (NO2) air pollution and asthma risk by early and middle childhood, and whether individual and community-level characteristics modify associations between air pollution exposure and asthma.Design, setting, and participantsThis cohort study included children enrolled in cohorts participating in the Children's Respiratory and Environmental Workgroup consortium. The birth cohorts were located throughout the US, recruited between 1987 and 2007, and followed up through age 11 years. The survival analysis was adjusted for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, neighborhood characteristics, and cohort. Statistical analysis was performed from February 2022 to December 2023.ExposureEarly-life exposures to PM2.5 and NO2 according to participants' birth address.Main outcomes and measuresCaregiver report of physician-diagnosed asthma through early (age 4 years) and middle (age 11 years) childhood.ResultsAmong 5279 children included, 1659 (31.4%) were Black, 835 (15.8%) were Hispanic, 2555 (48.4%) where White, and 229 (4.3%) were other race or ethnicity; 2721 (51.5%) were male and 2596 (49.2%) were female; 1305 children (24.7%) had asthma by 11 years of age and 954 (18.1%) had asthma by 4 years of age. Mean values of pollutants over the first 3 years of life were associated with asthma incidence. A 1 IQR increase in NO2 (6.1 μg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.25 [95% CI, 1.03-1.52]) and children younger than 11 years (HR, 1.22 [95% CI, 1.04-1.44]). A 1 IQR increase in PM2.5 (3.4 μg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.31 [95% CI, 1.04-1.66]) and children younger than 11 years (OR, 1.23 [95% CI, 1.01-1.50]). Associations of PM2.5 or NO2 with asthma were increased when mothers had less than a high school diploma, among Black children, in communities with fewer child opportunities, and in census tracts with higher percentage Black population and population density; for example, there was a significantly higher association between PM2.5 and asthma incidence by younger than 5 years of age in Black children (HR, 1.60 [95% CI, 1.15-2.22]) compared with White children (HR, 1.17 [95% CI, 0.90-1.52]).Conclusions and relevanceIn this cohort study, early life air pollution was associated with increased asthma incidence by early and middle childhood, with higher risk among minoritized families living in urban communities characterized by fewer opportunities and resources and multiple environmental coexposures. Reducing asthma risk in the US requires air pollution regulation and reduction combined with greater environmental, educational, and health equity at the community level.

Project description:Background: Current levels of traffic-related air pollution (TRAP) are associated with the development of childhood asthma, although some inconsistencies and heterogeneity remain. An important part of the uncertainty in studies of TRAP-associated asthma originates from uncertainties in the TRAP exposure assessment and assignment methods. In this work, we aim to systematically review the exposure assessment methods used in the epidemiology of TRAP and childhood asthma, highlight recent advances, remaining research gaps and make suggestions for further research. Methods: We systematically reviewed epidemiological studies published up until 8 September 2016 and available in Embase, Ovid MEDLINE (R), and "Transport database". We included studies which examined the association between children's exposure to TRAP metrics and their risk of "asthma" incidence or lifetime prevalence, from birth to the age of 18 years old. Results: We found 42 studies which examined the associations between TRAP and subsequent childhood asthma incidence or lifetime prevalence, published since 1999. Land-use regression modelling was the most commonly used method and nitrogen dioxide (NO₂) was the most commonly used pollutant in the exposure assessments. Most studies estimated TRAP exposure at the residential address and only a few considered the participants' mobility. TRAP exposure was mostly assessed at the birth year and only a few studies considered different and/or multiple exposure time windows. We recommend that further work is needed including e.g., the use of new exposure metrics such as the composition of particulate matter, oxidative potential and ultra-fine particles, improved modelling e.g., by combining different exposure assessment models, including mobility of the participants, and systematically investigating different exposure time windows. Conclusions: Although our previous meta-analysis found statistically significant associations for various TRAP exposures and subsequent childhood asthma, further refinement of the exposure assessment may improve the risk estimates, and shed light on critical exposure time windows, putative agents, underlying mechanisms and drivers of heterogeneity.

Project description:BackgroundRecent studies suggest that household endotoxin and allergens can modify the impact of air pollutants on development of asthma; however, epidemiological evidence is limited and conflicting.ObjectivesTo investigate whether pet ownership modified the association between ambient air pollution and asthma in children.MethodsWe conducted a population-based cross-sectional study, the Seven Northeast Cities Study in China and recruited a total of 59,754 children from 94 schools during 2012-2013. Long-term air pollutant concentrations, including airborne particulate matter with a diameter of 1 μm or less (PM1 ), PM2.5 , PM10 , and nitrogen dioxide (NO2 ) from 2009 to 2012 were estimated using a random forest model. We collected information of respiratory health in children using the Epidemiologic Standardization Project Questionnaire of the American Thoracic Society (ATS-DLD-78-A). Regression models were used to evaluate associations between pet ownership and air pollution on asthma after adjusting for potential covariates.ResultsExposure to increasing levels of air pollutants was associated with higher prevalence of asthma, but associations were significantly attenuated in children who owned pets. For example, compared to children without pets, those who owned pets did not have an increased risk of symptoms of asthma (odds ratio, 1.01, 95% confidence interval: 0.78, 1.30), wheeze (0.96, 95% confidence interval [CI]: 0.76, 1.21), and cough (1.01, 95% CI: 0.87, 1.18) for each 10 µg/m3 increase in PM1 (P-int < 0.05). Similar trends were observed for other air pollutants. Dog and bird ownership decreased the associations of asthma and cough with air pollutant exposure. The main findings were consistent with a series of sensitivity analyses.ConclusionCurrent pet ownership may reduce the adverse impact of long-term air pollution on childhood asthma. Longitudinal studies are needed to confirm this finding which could have important implications for public health.

Dataset Information

Genome-Wide Interaction Analysis of Air Pollution Exposure and Childhood Asthma with Functional Follow-up.

Rationale

Objectives

Methods

Measurements and main results

Conclusions

Publications

Genome-Wide Interaction Analysis of Air Pollution Exposure and Childhood Asthma with Functional Follow-up.

Similar Datasets

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