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

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

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

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 doctor's diagnosis 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 and CAPPS/SAGE (n=1,602 and 186 subjects, respectively). We assessed eQTL effects in human lung specimens and blood, as well as associations between air pollution exposure, methylation and transcriptomic patterns. MEASUREMENTS AND MAIN RESULTS: In the European cohorts, 186 SNPs had an interaction p-value<1x10(-4) and look-up evaluation of these disclosed eight SNPs in four loci with interaction p<0.05 in the large CHS study, but not in CAPPS/SAGE. Three SNPs within ADCY2 showed same direction of interaction effect, and were found to influence ADCY2 gene expression in peripheral blood (p=4.50x10(-4)). One other SNP with p<0.05 for interaction in CHS, rs686237, strongly influenced B4GALT5 expression in lung tissue (p=1.18x10(-17)). Air pollution exposure was associated with differential DLG2 methylation and expression. CONCLUSION: Our results indicate that gene-environment interactions are important for asthma development and provide supportive evidence for interaction with air pollution for ADCY2, B4GALT5 and DLG2

Exposure to residential air pollution and physician diagnosis of otitis media during the first two years of life in British Columbia, Canada

Otitis media is the leading reason children visit their doctor or consume antibiotics. It has been postulated that ambient air pollution is a risk factor for otitis, based on the known association with environmental tobacco smoke and a number of recent studies. This research utilized administrative data to identify and follow a population-based birth cohort of 59,917 children, born during 1999-2000 in southwestern British Columbia. The incidence and recurrence of otitis media was characterized during the first three years of life and available information on risk factors were assessed. Air pollution exposures (CO, NO, NO₂, O₃, PM₂.₅, PM₁₀, SO₂, black carbon, woodsmoke, point source and road proximity) were estimated for the first 24 months of life using ambient monitoring data, temporally adjusted land use regression models and proximity measures; and assigned to children based on residential postal code. The relationship between physician visits for otitis media and 2-month average pollutant exposures was assessed longitudinally. Finally, the economic burden of otitis media attributable to air pollution was calculated using data from the universal healthcare system and estimates from the literature. Otitis media incidence was relatively low (42% at 2years; 49% at 3years) compared with previous studies and peaked in the winter and at 8-10 months of age. Male gender, First Nations status and low socio-economic status were identified as strong risk factors for otitis media in this population. In analyses that included air pollution, CO, NO, NO₂ and woodsmoke were independent risk factors before seasonal adjustment; and NO, PM₂.₅ and woodsmoke were independent risk factors after seasonal adjustment. For this population, the cost of otitis media attributable to woodsmoke was valued at (2003) $420,464. Associations were found between otitis media and some air pollutants in a large birth cohort with relatively low ambient air pollution exposure. Null or protective associations (SO₂, O₃, black carbon) may be partially explained by temporal and spatial correlations between pollutants and otitis media. If the associations observed in this study are causal, the substantial economic burden attributable to air pollution suggests that it be considered a modifiable risk factor for this important childhood disease.Medicine, Faculty ofPopulation and Public Health (SPPH), School ofGraduat

GSTP1 and TNF Gene variants and associations between air pollution and incident childhood asthma: the traffic, asthma and genetics (TAG) study.

Genetics may partially explain observed heterogeneity in associations between traffic-related air pollution and incident asthma.Our aim was to investigate the impact of gene variants associated with oxidative stress and inflammation on associations between air pollution and incident childhood asthma.Traffic-related air pollution, asthma, wheeze, gene variant, and potential confounder data were pooled across six birth cohorts. Parents reported physician-diagnosed asthma and wheeze from birth to 7-8 years of age (confirmed by pediatric allergist in two cohorts). Individual estimates of annual average air pollution [nitrogen dioxide (NO2), particulate matter <= 2.5 ?m (PM2.5), PM2.5 absorbance, ozone] were assigned to each child's birth address using land use regression, atmospheric modeling, and ambient monitoring data. Effect modification by variants in GSTP1 (rs1138272/Ala114Val and rs1695/IIe105Val) and TNF (rs1800629/G-308A) was investigated.Data on asthma, wheeze, potential confounders, at least one SNP of interest, and NO2 were available for 5,115 children. GSTP1 rs1138272 and TNF rs1800629 SNPs were associated with asthma and wheeze, respectively. In relation to air pollution exposure, children with one or more GSTP1 rs1138272 minor allele were at increased risk of current asthma [odds ratio (OR) = 2.59; 95% CI: 1.43, 4.68 per 10 ?g/m3 NO2] and ever asthma (OR = 1.64; 95% CI: 1.06, 2.53) compared with homozygous major allele carriers (OR = 0.95; 95% CI: 0.68, 1.32 for current and OR = 1.20; 95% CI: 0.98, 1.48 for ever asthma; Bonferroni-corrected interaction p = 0.04 and 0.01, respectively). Similarly, for GSTP1 rs1695, associations between NO2 and current and ever asthma had ORs of 1.43 (95% CI: 1.03, 1.98) and 1.36 (95% CI: 1.08, 1.70), respectively, for minor allele carriers compared with ORs of 0.82 (95% CI: 0.52, 1.32) and 1.12 (95% CI: 0.84, 1.49) for homozygous major allele carriers (Bonferroni-corrected interaction p-values 0.48 and 0.09). There were no clear differences by TNF genotype.Children carrying GSTP1 rs1138272 or rs1695 minor alleles may constitute a susceptible population at increased risk of asthma associated with air pollution

Traffic, asthma and genetics: combining international birth cohort data to examine genetics as a mediator of traffic-related air pollution's impact on childhood asthma.

Associations between traffic-related air pollution and incident childhood asthma can be strengthened by analysis of gene-environment interactions, but studies have typically been limited by lack of study power. We combined data from six birth cohorts on: asthma, eczema and allergic rhinitis to 7/8 years, and candidate genes. Individual-level assessment of traffic-related air pollution exposure was estimated using land use regression or dispersion modeling. A total of 11,760 children were included in the Traffic, Asthma and Genetics (TAG) Study; 6.3 % reported physician-diagnosed asthma at school-age, 16.0 % had asthma at anytime during childhood, 14.1 % had allergic rhinitis at school-age, 10.0 % had eczema at school-age and 33.1 % were sensitized to any allergen. For GSTP1 rs1138272, the prevalence of heterozygosity was 16 % (range amongst individual cohorts, 11-17 %) and homozygosity for the minor allele was 1 % (0-2 %). For GSTP1 rs1695, the prevalence of heterozygosity was 45 % (40-48 %) and homozygosity for the minor allele, 12 % (10-12 %). For TNF rs1800629, the prevalence of heterozygosity was 29 % (25-32 %) and homozygosity for the minor allele, 3 % (1-3 %). TAG comprises a rich database, the largest of its kind, for investigating the effect of genotype on the association between air pollution and childhood allergic disease

Synthèse des données probantes - Évaluation de la communication des risques en présence de changements climatiques et de phénomènes météorologiques extrêmes : examen de la portée

Introduction. La communication des risques au public demeure un défi pour les professionnels de la santé publique oeuvrant dans le secteur des changements climatiques. Nous avons effectué un examen de la portée de la littérature sur l’évaluation de la communication des risques en présence de phénomènes météorologiques extrêmes et de changements climatiques dans le but de créer des messages en matière de santé publique à l’échelle locale conformes aux exigences des Normes de santé publique de l’Ontario (NSPO). Ces normes ont été mises à jour en 2018 pour inclure la communication efficace de messages sur les changements climatiques et les phénomènes météorologiques extrêmes. Méthodologie. Des spécialistes en bibliothéconomie ont établi des stratégies de recherche pour recenser les publications universitaires revues par des pairs et la littérature grise dans plusieurs bases de données bibliographiques (Medline, Embase, Scopus et CINAHL) et dans les moteurs de recherche Google nationaux. Cette stratégie de recherche a été validée lors d’un atelier avec des experts et des intervenants communautaires spécialisés en environnement, en santé, en gestion des urgences et en communication des risques. Résultats. Au total, 43 articles ont été retenus. Ces articles traitaient principalement des changements climatiques (n = 22), des inondations (n = 12), des ouragans (n = 5), de la chaleur extrême (n = 2) et des incendies de forêt (n = 2). Les études provenaient principalement des États-Unis (n = 14), de l’Europe (n = 6) et du Canada (n = 5). Conclusion. Pour satisfaire aux NSPO de 2018, les professionnels de la santé publique doivent communiquer efficacement les risques afin d’encourager la prise de mesures efficaces à l’échelle locale aptes à atténuer les effets des phénomènes météorologiques extrêmes et des changements climatiques. D’après notre examen de la portée, les efforts de communication des risques durant les phénomènes météorologiques extrêmes de courte durée semblent plus efficaces que les efforts de communication des risques liés aux changements climatiques. Cela pourrait constituer une occasion unique pour les intervenants en santé publique d’appliquer les stratégies couramment utilisées pour les phénomènes météorologiques extrêmes aux changements climatiques

Evidence synthesis - Evaluating risk communication during extreme weather and climate change: a scoping review

Introduction Communicating risk to the public continues to be a challenge for public health practitioners working in the area of climate change. We conducted a scoping literature review on the evaluation of risk communication for extreme weather and climate change to inform local public health messaging, consistent with requirements under the Ontario Public Health Standards (OPHS), which were updated in 2018 to include effective communication regarding climate change and extreme weather. Methods Search strategies were developed by library information specialists and used to retrieve peer-reviewed academic and grey literature from bibliographic databases (Medline, Embase, Scopus and CINAHL) and Google country specific searches, respectively. The search strategy was validated through a workshop with experts and community stakeholders, with expertise in environment, health, emergency management and risk communication. Results A total of 43 articles were included. These articles addressed issues such as: climate change (n = 22), flooding (n = 12), hurricane events (n = 5), extreme heat (n = 2), and wild fires (n = 2). Studies were predominantly from the US (n = 14), Europe (n = 6) and Canada (n = 5). Conclusion To meet the OPHS 2018, public health practitioners need to engage in effective risk communication to motivate local actions that mitigate the effects of extreme weather and climate change. Based on the scoping review, risk communication efforts during short-term extreme weather events appear to be more effective than efforts to communicate risk around climate change. This distinction could highlight a unique opportunity for public health to adapt strategies commonly used for extreme weather to climate change. </sec