Dataset Information

Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure.

ABSTRACT: Prenatal exposure to air pollution is considered to be associated with adverse effects on child health. This may partly be mediated by mechanisms related to DNA methylation.We investigated associations between exposure to air pollution, using nitrogen dioxide (NO2) as marker, and epigenome-wide cord blood DNA methylation.We meta-analyzed the associations between NO2 exposure at residential addresses during pregnancy and cord blood DNA methylation (Illumina 450K) in four European and North American studies (n = 1,508) with subsequent look-up analyses in children ages 4 (n = 733) and 8 (n = 786) years. Additionally, we applied a literature-based candidate approach for antioxidant and anti-inflammatory genes. To assess influence of exposure at the transcriptomics level, we related mRNA expression in blood cells to NO2 exposure in 4- (n = 111) and 16-year-olds (n = 239).We found epigenome-wide significant associations [false discovery rate (FDR) p < 0.05] between maternal NO2 exposure during pregnancy and DNA methylation in newborns for 3 CpG sites in mitochondria-related genes: cg12283362 (LONP1), cg24172570 (3.8 kbp upstream of HIBADH), and cg08973675 (SLC25A28). The associations with cg08973675 methylation were also significant in the older children. Further analysis of antioxidant and anti-inflammatory genes revealed differentially methylated CpGs in CAT and TPO in newborns (FDR p < 0.05). NO2 exposure at the time of biosampling in childhood had a significant impact on CAT and TPO expression.NO2 exposure during pregnancy was associated with differential offspring DNA methylation in mitochondria-related genes. Exposure to NO2 was also linked to differential methylation as well as expression of genes involved in antioxidant defense pathways. Citation: Gruzieva O, Xu CJ, Breton CV, Annesi-Maesano I, Antó JM, Auffray C, Ballereau S, Bellander T, Bousquet J, Bustamante M, Charles MA, de Kluizenaar Y, den Dekker HT, Duijts L, Felix JF, Gehring U, Guxens M, Jaddoe VV, Jankipersadsing SA, Merid SK, Kere J, Kumar A, Lemonnier N, Lepeule J, Nystad W, Page CM, Panasevich S, Postma D, Slama R, Sunyer J, Söderhäll C, Yao J, London SJ, Pershagen G, Koppelman GH, Melén E. 2017. Epigenome-wide meta-analysis of methylation in children related to prenatal NO2 air pollution exposure. Environ Health Perspect 125:104-110;?http://dx.doi.org/10.1289/EHP36.

SUBMITTER: Gruzieva O

PROVIDER: S-EPMC5226705 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure.

Gruzieva Olena O Xu Cheng-Jian CJ Breton Carrie V CV Annesi-Maesano Isabella I Antó Josep M JM Auffray Charles C Ballereau Stéphane S Bellander Tom T Bousquet Jean J Bustamante Mariona M Charles Marie-Aline MA de Kluizenaar Yvonne Y den Dekker Herman T HT Duijts Liesbeth L Felix Janine F JF Gehring Ulrike U Guxens Mònica M Jaddoe Vincent V W VV Jankipersadsing Soesma A SA Merid Simon Kebede SK Kere Juha J Kumar Ashish A Lemonnier Nathanael N Lepeule Johanna J Nystad Wenche W Page Christian Magnus CM Panasevich Sviatlana S Postma Dirkje D Slama Rémy R Sunyer Jordi J Söderhäll Cilla C Yao Jin J London Stephanie J SJ Pershagen Göran G Koppelman Gerard H GH Melén Erik E

Environmental health perspectives 20160722 1

<h4>Background</h4>Prenatal exposure to air pollution is considered to be associated with adverse effects on child health. This may partly be mediated by mechanisms related to DNA methylation.<h4>Objectives</h4>We investigated associations between exposure to air pollution, using nitrogen dioxide (NO2) as marker, and epigenome-wide cord blood DNA methylation.<h4>Methods</h4>We meta-analyzed the associations between NO2 exposure at residential addresses during pregnancy and cord blood DNA methyla ...[more]

PMID: 27448387

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Project description:BackgroundPrenatal exposure to air pollution has been associated with childhood respiratory disease and other adverse outcomes. Epigenetics is a suggested link between exposures and health outcomes.ObjectivesWe aimed to investigate associations between prenatal exposure to particulate matter (PM) with diameter [Formula: see text] ([Formula: see text]) or [Formula: see text] ([Formula: see text]) and DNA methylation in newborns and children.MethodsWe meta-analyzed associations between exposure to [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]) at maternal home addresses during pregnancy and newborn DNA methylation assessed by Illumina Infinium HumanMethylation450K BeadChip in nine European and American studies, with replication in 688 independent newborns and look-up analyses in 2,118 older children. We used two approaches, one focusing on single cytosine-phosphate-guanine (CpG) sites and another on differentially methylated regions (DMRs). We also related PM exposures to blood mRNA expression.ResultsSix CpGs were significantly associated [false discovery rate (FDR) [Formula: see text]] with prenatal [Formula: see text] and 14 with [Formula: see text] exposure. Two of the [Formula: see text] CpGs mapped to FAM13A (cg00905156) and NOTCH4 (cg06849931) previously associated with lung function and asthma. Although these associations did not replicate in the smaller newborn sample, both CpGs were significant ([Formula: see text]) in 7- to 9-y-olds. For cg06849931, however, the direction of the association was inconsistent. Concurrent [Formula: see text] exposure was associated with a significantly higher NOTCH4 expression at age 16 y. We also identified several DMRs associated with either prenatal [Formula: see text] and or [Formula: see text] exposure, of which two [Formula: see text] DMRs, including H19 and MARCH11, replicated in newborns.ConclusionsSeveral differentially methylated CpGs and DMRs associated with prenatal PM exposure were identified in newborns, with annotation to genes previously implicated in lung-related outcomes. https://doi.org/10.1289/EHP4522.

Project description:ImportanceDNA methylation (DNAm) provides a plausible mechanism by which adverse exposures become embodied and contribute to health inequities, due to its role in genome regulation and responsiveness to social and biophysical exposures tied to societal context. However, scant epigenome-wide association studies (EWAS) have included structural and lifecourse measures of exposure, especially in relation to structural discrimination.ObjectiveOur study tests the hypothesis that DNAm is a mechanism by which racial discrimination, economic adversity, and air pollution become biologically embodied.DesignA series of cross-sectional EWAS, conducted in My Body My Story (MBMS, biological specimens collected 2008-2010, DNAm assayed in 2021); and the Multi Ethnic Study of Atherosclerosis (MESA; biological specimens collected 2010-2012, DNAm assayed in 2012-2013); using new georeferenced social exposure data for both studies (generated in 2022).SettingMBMS was recruited from four community health centers in Boston; MESA was recruited from four field sites in: Baltimore, MD; Forsyth County, NC; New York City, NY; and St. Paul, MN.ParticipantsTwo population-based samples of US-born Black non-Hispanic (Black NH), white non-Hispanic (white NH), and Hispanic individuals (MBMS; n=224 Black NH and 69 white NH) and (MESA; n=229 Black NH, n=555 white NH and n=191 Hispanic).ExposuresEight social exposures encompassing racial discrimination, economic adversity, and air pollution.Main outcomeGenome-wide changes in DNAm, as measured using the Illumina EPIC BeadChip (MBMS; using frozen blood spots) and Illumina 450k BeadChip (MESA; using purified monocytes). Our hypothesis was formulated after data collection.ResultsWe observed the strongest associations with traffic-related air pollution (measured via black carbon and nitrogen oxides exposure), with evidence from both studies suggesting that air pollution exposure may induce epigenetic changes related to inflammatory processes. We also found suggestive associations of DNAm variation with measures of structural racial discrimination (e.g., for Black NH participants, born in a Jim Crow state; adult exposure to racialized economic residential segregation) situated in genes with plausible links to effects on health.Conclusions and relevanceOverall, this work suggests that DNAm is a biological mechanism through which structural racism and air pollution become embodied and may lead to health inequities.

Project description:Air pollution might affect atherosclerosis through DNA methylation changes in cells crucial to atherosclerosis, such as monocytes. We conducted an epigenome-wide study of DNA methylation in CD14+ monocytes and long-term ambient air pollution exposure in adults participating in the Multi-Ethnic Study of Atherosclerosis (MESA). We also assessed the association between differentially methylated signals and cis-gene expression. Using spatiotemporal models, one-year average concentrations of outdoor fine particulate matter (PM2.5) and oxides of nitrogen (NOX) were estimated at participants' homes. We assessed DNA methylation and gene expression using Illumina 450k and HumanHT-12 v4 Expression BeadChips, respectively (n = 1,207). We used bump hunting and site-specific approaches to identify differentially methylated signals (false discovery rate of 0.05) and used linear models to assess associations between differentially methylated signals and cis-gene expression. Four differentially methylated regions (DMRs) located on chromosomes 5, 6, 7, and 16 (within or near SDHAP3, ZFP57, HOXA5, and PRM1, respectively) were associated with PM2.5. The DMRs on chromosomes 5 and 6 also associated with NOX. The DMR on chromosome 5 had the smallest p-value for both PM2.5 (p = 1.4×10-6) and NOX (p = 7.7×10-6). Three differentially methylated CpGs were identified for PM2.5, and cg05926640 (near TOMM20) had the smallest p-value (p = 5.6×10-8). NOX significantly associated with cg11756214 within ZNF347 (p = 5.6×10-8). Several differentially methylated signals were also associated with cis-gene expression. The DMR located on chromosome 7 was associated with the expression of HOXA5, HOXA9, and HOXA10. The DMRs located on chromosomes 5 and 16 were associated with expression of MRPL36 and DEXI, respectively. The CpG cg05926640 was associated with expression of ARID4B, IRF2BP2, and TOMM20. We identified differential DNA methylation in monocytes associated with long-term air pollution exposure. Methylation signals associated with gene expression might help explain how air pollution contributes to cardiovascular disease.

Project description:ImportanceAir pollution is associated with structural brain changes, disruption of neurogenesis, and neurodevelopmental disorders. The association between prenatal exposure to ambient air pollution and risk of cerebral palsy (CP), which is the most common motor disability in childhood, has not been thoroughly investigated.ObjectiveTo evaluate the associations between prenatal residential exposure to ambient air pollution and risk of CP among children born at term gestation in a population cohort in Ontario, Canada.Design, setting, and participantsPopulation-based cohort study in Ontario, Canada using linked, province-wide health administrative databases. Participants were singleton full term births (≥37 gestational weeks) born in Ontario hospitals between April 1, 2002, and March 31, 2017. Data were analyzed from January to December 2022.ExposuresWeekly average concentrations of ambient fine particulate matter with a diameter 2.5 μm (PM2.5) or smaller, nitrogen dioxide (NO2), and ozone (O3) during pregnancy assigned by maternal residence reported at delivery from satellite-based estimates and ground-level monitoring data.Main outcome and measuresCP cases were ascertained by a single inpatient hospitalization diagnosis or at least 2 outpatient diagnoses for children from birth to age 18 years.ResultsThe present study included 1 587 935 mother-child pairs who reached term gestation, among whom 3170 (0.2%) children were diagnosed with CP. The study population had a mean (SD) maternal age of 30.1 (5.6) years and 811 745 infants (51.1%) were male. A per IQR increase (2.7 μg/m3) in prenatal ambient PM2.5 concentration was associated with a cumulative hazard ratio (CHR) of 1.12 (95% CI, 1.03-1.21) for CP. The CHR in male infants (1.14; 95% CI, 1.02-1.26) was higher compared with the CHR in female infants (1.08; 95% CI, 0.96-1.22). No specific window of susceptibility was found for prenatal PM2.5 exposure and CP in the study population. No associations or windows of susceptibility were found for prenatal NO2 or O3 exposure and CP risk.Conclusions and relevanceIn this large cohort study of singleton full term births in Canada, prenatal ambient PM2.5 exposure was associated with an increased risk of CP in offspring. Further studies are needed to explore this association and its potential biological pathways, which could advance the identification of environmental risk factors of CP in early life.

Project description:BackgroundTelomere length is a molecular marker of biological aging.ObjectiveHere we investigated whether early-life exposure to residential air pollution was associated with leukocyte telomere length (LTL) at 8 y of age.MethodsIn a multicenter European birth cohort study, HELIX (Human Early Life Exposome) ([Formula: see text]), we estimated prenatal and 1-y childhood exposure to nitrogen dioxide ([Formula: see text]), particulate matter with aerodynamic diameter [Formula: see text] ([Formula: see text]), and proximity to major roads. Average relative LTL was measured using quantitative real-time polymerase chain reaction (qPCR). Effect estimates of the association between LTL and prenatal, 1-y childhood air pollution, and proximity to major roads were calculated using multiple linear mixed models with a random cohort effect and adjusted for relevant covariates.ResultsLTL was inversely associated with prenatal and 1-y childhood [Formula: see text] and [Formula: see text] exposures levels. Each standard deviation (SD) increase in prenatal [Formula: see text] was associated with a [Formula: see text] (95% CI: [Formula: see text], [Formula: see text]) change in LTL. Prenatal [Formula: see text] was nonsignificantly associated with LTL ([Formula: see text] per SD increase; 95% CI: [Formula: see text], 0.6). For each SD increment in 1-y childhood [Formula: see text] and [Formula: see text] exposure, LTL shortened by [Formula: see text] (95% CI: [Formula: see text], [Formula: see text]) and [Formula: see text] (95% CI: [Formula: see text], 0.1), respectively. Each doubling in residential distance to nearest major road during childhood was associated with a 1.6% (95% CI: 0.02, 3.1) lengthening in LTL.ConclusionLower exposures to air pollution during pregnancy and childhood were associated with longer telomeres in European children at 8 y of age. These results suggest that reductions in traffic-related air pollution may promote molecular longevity, as exemplified by telomere length, from early life onward. https://doi.org/10.1289/EHP4148.

Dataset Information

Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure.

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Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure.

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