Methylome-wide association study provides evidence of particulate matter air pollution-associated DNA methylation.
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ABSTRACT: Background
DNA methylation (DNAm) may contribute to processes that underlie associations between air pollution and poor health. Therefore, our objective was to evaluate associations between DNAm and ambient concentrations of particulate matter (PM) ≤2.5, ≤10, and 2.5-10 μm in diameter (PM2.5; PM10; PM2.5-10).Methods
We conducted a methylome-wide association study among twelve cohort- and race/ethnicity-stratified subpopulations from the Women's Health Initiative and the Atherosclerosis Risk in Communities study (n = 8397; mean age: 61.5 years; 83% female; 45% African American; 9% Hispanic/Latino American). We averaged geocoded address-specific estimates of daily and monthly mean PM concentrations over 2, 7, 28, and 365 days and 1 and 12 months before exams at which we measured leukocyte DNAm in whole blood. We estimated subpopulation-specific, DNAm-PM associations at approximately 485,000 Cytosine-phosphate-Guanine (CpG) sites in multi-level, linear, mixed-effects models. We combined subpopulation- and site-specific estimates in fixed-effects, inverse variance-weighted meta-analyses, then for associations that exceeded methylome-wide significance and were not heterogeneous across subpopulations (P < 1.0 × 10-7; PCochran's Q > 0.10), we characterized associations using publicly accessible genomic databases and attempted replication in the Cooperative Health Research in the Region of Augsburg (KORA) study.Results
Analyses identified significant DNAm-PM associations at three CpG sites. Twenty-eight-day mean PM10 was positively associated with DNAm at cg19004594 (chromosome 20; MATN4; P = 3.33 × 10-8). One-month mean PM10 and PM2.5-10 were positively associated with DNAm at cg24102420 (chromosome 10; ARPP21; P = 5.84 × 10-8) and inversely associated with DNAm at cg12124767 (chromosome 7; CFTR; P = 9.86 × 10-8). The PM-sensitive CpG sites mapped to neurological, pulmonary, endocrine, and cardiovascular disease-related genes, but DNAm at those sites was not associated with gene expression in blood cells and did not replicate in KORA.Conclusions
Ambient PM concentrations were associated with DNAm at genomic regions potentially related to poor health among racially, ethnically and environmentally diverse populations of U.S. women and men. Further investigation is warranted to uncover mechanisms through which PM-induced epigenomic changes may cause disease.
SUBMITTER: Gondalia R
PROVIDER: S-EPMC6754789 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundEpigenetic age, as defined by DNA methylation, may be influenced by air pollution exposure.ObjectiveTo evaluate the relationship between NO2, particulate matter (PM), PM components and accelerated epigenetic age.MethodsIn a sample of non-Hispanic white women living in the contiguous U.S. (n = 2747), we estimated residential exposure to PM2.5, PM10 and NO2 using a model incorporating land-use regression and kriging. Predictive k-means was used to assign participants to clusters representing different PM2.5 component profiles. We measured DNA methylation (DNAm) in blood using the Illumina's Infinium HumanMethylation450 BeadChip and calculated DNAm age using the Hannum, Horvath and Levine epigenetic clocks. Age acceleration was defined based on residuals after regressing DNAm age on chronological age. We estimated associations between interquartile range (IQR) increases in pollutants and age acceleration using linear regression. For PM2.5, we stratified by cluster membership. We examined epigenome-wide associations using robust linear regression models corrected with false discovery rate q-values.ResultsNO2 was inversely associated with age acceleration using the Hannum clock (β = -0.24, 95% CI: -0.47, -0.02). No associations were observed for PM10. For PM2.5, the association with age acceleration varied by PM2.5 component cluster. For example, with the Levine clock, an IQR increase in PM2.5 was associated with an over 6-year age acceleration in a cluster that has relatively high fractions of crustal elements relative to overall PM2.5 (β = 6.57, 95% CI: 2.68, 10.47), and an almost 2-year acceleration in a cluster characterized by relatively low sulfur fractions (β = 1.88, 95% CI: 0.51, 3.25). In a cluster distinguished by lower relative nitrate concentrations, PM2.5 was inversely associated with age acceleration (β = -1.33, 95% CI: -2.43, -0.23). Across the epigenome, NO2 was associated with methylation at 2 CpG sites.ConclusionAir pollution was associated with epigenetic age, a marker of mortality and disease risk, among certain PM2.5 component profiles.
| S-EPMC6754788 | biostudies-literature
Project description:BackgroundAmbient particulate matter (PM) has been associated with mitochondrial damage and dysfunction caused by excessive oxidative stress, but the associations between long-term PM exposure and leukocyte mitochondrial DNA copy number (mtDNAcn), a biomarker of mitochondrial dysfunction due to oxidative stress, are less studied.ObjectivesTo investigate the associations between short-, intermediate- and long-term exposure (1-, 3- and 12-months) to different size fractions of PM (PM2.5, PM2.5-10 and PM10) and leukocyte mtDNAcn in a cross-sectional study.MethodsThe associations between each of the PM exposure metrics with z scores of log-transformed mtDNAcn were examined using generalized linear regression models in 2758 female participants from the Nurses' Health Study (NHS). Monthly exposures to PM were estimated from spatio-temporal prediction models matched to each participants' address history. Potential effect modification by selected covariates was examined using multiplicative interaction terms and subgroup analyses.ResultsIn single-size fraction models, increases in all size fractions of PM were associated with decreases in mtDNAcn, although only models with longer averages of PM2.5 reached statistical significance. For example, an interquartile range (IQR) increase in 12-month average ambient PM2.5 (5.5 μg/m3) was associated with a 0.07 [95% confidence interval (95% CI): -0.13, -0.01; p-value = 0.02] decrease in mtDNAcn z score in both basic- and multivariable-adjusted models. Associations for PM2.5 were stronger after controlling for PM2.5-10 in two size-fraction models.ConclusionsOur study suggests that long-term exposure to ambient PM2.5 is associated with decreased mtDNAcn in healthy women.
| S-EPMC7419671 | biostudies-literature
Project description:ImportanceIncreased levels of ambient fine particulate matter (PM2.5) air pollution are associated with increased risks for detrimental health outcomes, but risks for patients with kidney transplants (KTs) remain unknown.ObjectiveTo investigate the association of PM2.5 exposure with KT outcomes.Design, setting, and participantsThis retrospective cohort study was conducted using data on patients who received KTs from 2004 to 2016 who were identified in the national US transplant registry and followed up through March 2021. Multiple databases were linked to obtain data on PM2.5 concentration, KT outcomes, and patient clinical, transplant, and contextual factors. Data were analyzed from April 2020 through July 2021.ExposuresExposures included post-KT time-dependent annual mean PM2.5 level (in 10 μg/m3) and mean PM2.5 level in the year before KT (ie, baseline levels) in quartiles, as well as baseline annual mean PM2.5 level (in 10 μg/m3).Main outcomes and measuresAcute kidney rejection (ie, rejection within 1 year after KT), time to death-censored graft failure, and time to all-cause death. Multivariable logistic regression for kidney rejection and Cox analyses with nonlinear assessment of exposure-response for death-censored graft failure and all-cause death were performed. The national burden of graft failure associated with PM2.5 levels greater than the Environmental Protection Agency recommended level of 12 μg/m3 was estimated.ResultsAmong 112 098 patients with KTs, 70 522 individuals (62.9%) were older than age 50 years at the time of KT, 68 117 (60.8%) were men, and the median (IQR) follow-up was 6.0 (3.9-8.9) years. There were 37 265 Black patients (33.2%), 17 047 Hispanic patients (15.2%), 48 581 White patients [43.3%]), and 9205 patients (8.2%) of other race or ethnicity. The median (IQR) baseline PM2.5 level was 9.8 (8.3-11.9) μg/m3. Increased baseline PM2.5 level, compared with quartile 1 baseline PM2.5 level, was not associated with higher odds of acute kidney rejection for quartile 2 (adjusted odds ratio [aOR], 0.99; 95% CI, 0.92-1.06) but was associated with increased odds for quartile 3 (aOR, 1.11; 95% CI, 1.04-1.20) and quartile 4 (aOR, 1.13; 95% CI, 1.05-1.23). Nonlinear assessment of exposure-response for graft failure and death showed no evidence for nonlinearity. Increased PM2.5 levels were associated with increased risk of death-censored graft failure (adjusted hazard ratio [aHR] per 10 μg/m3 increase, 1.17; 95% CI, 1.09-1.25) and all-cause death (aHR per 10 μg/m3 increase, 1.21; 95% CI, 1.14-1.28). The national burden of death-censored graft failure associated with PM2.5 above 12 μg/m3 was 57 failures (95% uncertainty interval, 48-67 failures) per year among patients with KTs.Conclusions and relevanceThis cohort study found that PM2.5 level was an independent risk factor associated with acute rejection, graft failure, and death among patients with KTs. These findings suggest that efforts toward decreasing levels of PM2.5 concentration may be associated with improved outcomes after KT.
| S-EPMC8498852 | biostudies-literature
Project description:Autism is a heterogeneous disorder with genetic and environmental factors likely contributing to its origins. Examination of hazardous pollutants has suggested the importance of air toxics in the etiology of autism, yet little research has examined its association with local levels of air pollution using residence-specific exposure assignments.To examine the relationship between traffic-related air pollution, air quality, and autism.This population-based case-control study includes data obtained from children with autism and control children with typical development who were enrolled in the Childhood Autism Risks from Genetics and the Environment study in California. The mother's address from the birth certificate and addresses reported from a residential history questionnaire were used to estimate exposure for each trimester of pregnancy and first year of life. Traffic-related air pollution was assigned to each location using a line-source air-quality dispersion model. Regional air pollutant measures were based on the Environmental Protection Agency's Air Quality System data. Logistic regression models compared estimated and measured pollutant levels for children with autism and for control children with typical development.Case-control study from California.A total of 279 children with autism and a total of 245 control children with typical development.Crude and multivariable adjusted odds ratios (AORs) for autism.Children with autism were more likely to live at residences that had the highest quartile of exposure to traffic-related air pollution, during gestation (AOR, 1.98 [95% CI, 1.20-3.31]) and during the first year of life (AOR, 3.10 [95% CI, 1.76-5.57]), compared with control children. Regional exposure measures of nitrogen dioxide and particulate matter less than 2.5 and 10 ?m in diameter (PM2.5 and PM10) were also associated with autism during gestation (exposure to nitrogen dioxide: AOR, 1.81 [95% CI, 1.37-3.09]; exposure to PM2.5: AOR, 2.08 [95% CI, 1.93-2.25]; exposure to PM10: AOR, 2.17 [95% CI, 1.49-3.16) and during the first year of life (exposure to nitrogen dioxide: AOR, 2.06 [95% CI, 1.37-3.09]; exposure to PM2.5: AOR, 2.12 [95% CI, 1.45-3.10]; exposure to PM10: AOR, 2.14 [95% CI, 1.46-3.12]). All regional pollutant estimates were scaled to twice the standard deviation of the distribution for all pregnancy estimates.Exposure to traffic-related air pollution, nitrogen dioxide, PM2.5, and PM10 during pregnancy and during the first year of life was associated with autism. Further epidemiological and toxicological examinations of likely biological pathways will help determine whether these associations are causal.
| S-EPMC4019010 | biostudies-literature
Project description:Particulate matter (PM) air pollution exposure has been associated with cancer incidence and mortality especially with lung cancer. The liver is another organ possibly affected by PM due to its role in detoxifying xenobiotics absorbed from PM. Various studies have investigated the mechanistic pathways between inhaled pollutants and liver damage, cancer incidence, and tumor progression. However, little is known about the effects of PM on liver cancer survival. Twenty thousand, two hundred and twenty-one California Cancer Registry patients with hepatocellular carcinoma (HCC) diagnosed between 2000 and 2009 were used to examine the effect of exposure to ambient PM with diameter <2.5 μm (PM2.5 ) on HCC survival. Cox proportional hazards models were used to estimate hazard ratios (HRs) relating PM2.5 to all-cause and liver cancer-specific mortality linearly and nonlinearly-overall and stratified by stage at diagnosis (local, regional and distant)-adjusting for potential individual and geospatial confounders.PM2.5 exposure after diagnosis was statistically significantly associated with HCC survival. After adjustment for potential confounders, the all-cause mortality HR associated with a 1 standard deviation (5.0 µg/m3 ) increase in PM2.5 was 1.18 (95% CI: 1.16-1.20); 1.31 (95% CI:1.26-1.35) for local stage, 1.19 (95% CI:1.14-1.23) for regional stage, and 1.05 (95% CI:1.01-1.10) for distant stage. These associations were nonlinear, with substantially larger HRs at higher exposures. The associations between liver cancer-specific mortality and PM2.5 were slightly attenuated compared to all-cause mortality, but with the same patterns.Exposure to elevated PM2.5 after the diagnosis of HCC may shorten survival, with larger effects at higher concentrations.
| S-EPMC5505313 | biostudies-literature
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.
| S-EPMC6792178 | biostudies-literature
Project description:Air pollution is a complex mixture of gaseous and particulate components, each of which has detrimental effects on human health. While the composition of air pollution varies greatly depending on the source, studies from across the world have consistently shown that air pollution is an important modifiable risk factor for significantly increased morbidity and mortality. Moreover, clinical studies have generally shown a greater impact of particulate matter (PM) air pollution on health than the gaseous components. PM has wide-ranging deleterious effects on human health, particularly on the cardiovascular system. Both acute and chronic exposure to PM air pollution is associated with increased risk of death from cardiovascular diseases including ischemic heart disease, heart failure, and ischemic/thrombotic stroke. Particulate matter has also been shown to be an important endocrine disrupter, contributing to the development of metabolic diseases such as obesity and diabetes mellitus, which themselves are risk factors for cardiovascular disease. While the epidemiological evidence for the deleterious effects of PM air pollution on health is increasingly accepted, newer studies are shedding light on the mechanisms by which PM exerts its toxic effects. A greater understanding of how PM exerts toxic effects on human health is required in order to prevent and minimize the deleterious health effects of this ubiquitous environmental hazard. Air pollution is a growing public health problem and mortality due to air pollution is expected to double by 2050. Here, we review the epidemiological evidence for the cardiovascular effects of PM exposure and discuss current understanding about the biological mechanisms, by which PM exerts toxic effects on cardiovascular system to induce cardiovascular disease.
| S-EPMC6250783 | biostudies-literature
Project description:Using daily fine particulate matter (PM2.5) composition data from the 2000-2005 U.S. EPA Chemical Speciation Network (CSN) for over 200 sites, we applied multivariate methods to identify and quantify the major fine particulate matter (PM2.5) source components in the U.S. Novel aspects of this work were: (1) the application of factor analysis (FA) to multi-city daily data, drawing upon both spatial and temporal variations of chemical species; and, (2) the exclusion of secondary components (sulfates, nitrates and organic carbon) from the source identification FA to more clearly discern and apportion the PM2.5 mass to primary emission source categories. For the quantification of source-related mass, we considered two approaches based upon the FA results: 1) using single key tracers for sources identified by FA in a mass regression; and, 2) applying Absolute Principal Component Analysis (APCA). In each case, we followed a two-stage mass regression approach, in which secondary components were first apportioned among the identified sources, and then mass was apportioned to the sources and to other secondary mass not explained by the individual sources. The major U.S. PM2.5 source categories identified via FA (and their key elements) were: Metals Industry (Pb, Zn); Crustal/Soil Particles (Ca, Si); Motor Vehicle Traffic (EC, NO2); Steel Industry (Fe, Mn); Coal Combustion (As, Se); Oil Combustion (V, Ni); Salt Particles (Na, Cl) and Biomass Burning (K). Nationwide spatial plots of the source-related PM2.5 impacts were confirmatory of the factor interpretations: ubiquitous sources, such as Traffic and Soil, were found to be spread across the nation, more unique sources (such as Steel and Metals Processing) being highest in select industrialized cities, Biomass Burning was highest in the U.S. Northwest, while Residual Oil combustion was highest in cities in the Northeastern U.S. and in cities with major seaports. The sum of these source contributions and the secondary PM2.5 components agreed well with the U.S. PM2.5 observed during the study period (mean=14.3 ug/m3; R2= 0.91). Apportionment regression analyses using single-element tracers for each source category gave results consistent with the APCA estimates. Comparisons of nearby sites indicated that the PM2.5 mass and the secondary aerosols were most homogenous spatially, while traffic PM2.5 and its tracer, EC, were among the most spatially representative of the source-related components. Comparison of apportionment results to a previous analysis of the 1979-1982 IP Network revealed similar and correlated major U.S. source category factors, albeit at lower levels than in the earlier period, suggesting a consistency in the U.S. spatial patterns of these source-related exposures over time, as well. These results indicate that applying source apportionment methods to the nationwide CSN can be an informative avenue for identifying and quantifying source components for the subsequent estimation of source-specific health effects, potentially contributing to more efficient regulation of PM2.5.
| S-EPMC3951912 | biostudies-literature
Project description:ImportanceThe health effects of exposure to particulate matter (PM) on male fertility remain unclear. Although PM exposure has been linked with semen quality, the results were inconsistent.ObjectiveTo examine the association of different size fractions of PM (<2.5 μm [PM2.5], 2.5-10 μm [PM2.5-10], and ≤10 μm [PM10]) exposure with semen quality in China.Design, setting, and participantsThis retrospective cohort study was conducted using data on men whose wives underwent assisted reproductive technology procedures in a tertiary hospital in Shanghai, China, from January 1, 2013, to December 31, 2019. Participants were from 340 prefecture-level cities of China and were followed up from the date of their first visit until December 31, 2019. Data were analyzed from December 1, 2020, to May 15, 2021.ExposuresExposure to PM2.5, PM2.5-10, and PM10 during the entire period (0-90 days before semen ejaculation) and key periods of sperm development (0-9, 10-14, and 70-90 days before semen ejaculation).Main outcomes and measuresSemen quality, including sperm count, concentration, and motility.ResultsA total of 33 876 men were included in the final analysis, with a mean (SD) age of 34.1 (5.7) years and large variation of PM exposure. For example, the median exposure to PM2.5 during the entire period of sperm development was 46.05 (IQR, 34.38-61.65) μg/m3. During the entire period of sperm development, exposures to higher levels of PM were significantly associated with lower total and progressive sperm motility. For total sperm motility, an IQR increase in PM2.5 exposure was associated with an estimated effect decrease of -3.60% (95% CI, -3.93% to -3.26%); an increase in PM2.5-10 exposure, with an estimated effect decrease of -0.45% (95% CI, -0.76% to -0.14%); and an increase in PM10 exposure, with an estimated effect decrease of -2.44% (95% CI, -2.91% to -1.96%). Similar results were observed for progressive motility. An IQR increase in PM2.5 or PM10 exposures was associated with an estimated effect decrease on sperm progressive motility of -1.87% (95% CI, -2.37% to -1.36%) and -1.05% (95% CI, -1.45% to -0.64%), respectively. However, no significant associations were observed between PM exposure during the entire period of sperm development and sperm count or concentration.Conclusions and relevanceThese findings suggest that PM exposure may adversely affect sperm motility and highlight the need to reduce ambient particulate air pollution exposure for reproductive-aged men.
| S-EPMC8855237 | biostudies-literature
Project description:Epidemiological studies have reported associations between particulate matter (PM) concentrations and cancer and respiratory and cardiovascular diseases. DNA methylation has been identified as a possible link but so far it has only been analyzed in candidate sites.We studied the association between DNA methylation and short- and mid-term air pollution exposure using genome-wide data and identified potential biological pathways for additional investigation.We collected whole blood samples from three independent studies-KORA F3 (2004-2005) and F4 (2006-2008) in Germany, and the Normative Aging Study (1999-2007) in the United States-and measured genome-wide DNA methylation proportions with the Illumina 450k BeadChip. PM concentration was measured daily at fixed monitoring stations and three different trailing averages were considered and regressed against DNA methylation: 2-day, 7-day and 28-day. Meta-analysis was performed to pool the study-specific results.Random-effect meta-analysis revealed 12 CpG (cytosine-guanine dinucleotide) sites as associated with PM concentration (1 for 2-day average, 1 for 7-day, and 10 for 28-day) at a genome-wide Bonferroni significance level (p ? 7.5E-8); 9 out of these 12 sites expressed increased methylation. Through estimation of I2 for homogeneity assessment across the studies, 4 of these sites (annotated in NSMAF, C1orf212, MSGN1, NXN) showed p > 0.05 and I2 < 0.5: the site from the 7-day average results and 3 for the 28-day average. Applying false discovery rate, p-value < 0.05 was observed in 8 and 1,819 additional CpGs at 7- and 28-day average PM2.5 exposure respectively.The PM-related CpG sites found in our study suggest novel plausible systemic pathways linking ambient PM exposure to adverse health effect through variations in DNA methylation.Panni T, Mehta AJ, Schwartz JD, Baccarelli AA, Just AC, Wolf K, Wahl S, Cyrys J, Kunze S, Strauch K, Waldenberger M, Peters A. 2016. A genome-wide analysis of DNA methylation and fine particulate matter air pollution in three study populations: KORA F3, KORA F4, and the Normative Aging Study. Environ Health Perspect 124:983-990;?http://dx.doi.org/10.1289/ehp.1509966.
| S-EPMC4937859 | biostudies-other