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dc.contributor.authorPlusquin, Michelle
dc.contributor.authorGuida, Florence
dc.contributor.authorPolidoro, Silvia
dc.contributor.authorVermeulen, Roel
dc.contributor.authorRaaschou-Nielsen, Ole
dc.contributor.authorCampanella, Gianluca
dc.contributor.authorHoek, Gerard
dc.contributor.authorKyrtopoulos, Soterios A
dc.contributor.authorGeorgiadis, Panagiotis
dc.contributor.authorNaccarati, Alessio
dc.contributor.authorSacerdote, Carlotta
dc.contributor.authorKrogh, Vittorio
dc.contributor.authorBas Bueno-de-Mesquita, H
dc.contributor.authorMonique Verschuren, W M
dc.contributor.authorSayols-Baixeras, Sergi
dc.contributor.authorPanni, Tommaso
dc.contributor.authorPeters, Annette
dc.contributor.authorHebels, Dennie G A J
dc.contributor.authorKleinjans, Jos
dc.contributor.authorVineis, Paolo
dc.contributor.authorChadeau-Hyam, Marc
dc.date.accessioned2018-01-09T13:10:22Z
dc.date.available2018-01-09T13:10:22Z
dc.date.issued2017-11
dc.identifier.citationDNA methylation and exposure to ambient air pollution in two prospective cohorts. 2017, 108:127-136 Environ Inten
dc.identifier.issn1873-6750
dc.identifier.pmid28843141
dc.identifier.doi10.1016/j.envint.2017.08.006
dc.identifier.urihttp://hdl.handle.net/10029/621081
dc.description.abstractLong-term exposure to air pollution has been associated with several adverse health effects including cardiovascular, respiratory diseases and cancers. However, underlying molecular alterations remain to be further investigated. The aim of this study is to investigate the effects of long-term exposure to air pollutants on (a) average DNA methylation at functional regions and, (b) individual differentially methylated CpG sites. An assumption is that omic measurements, including the methylome, are more sensitive to low doses than hard health outcomes. This study included blood-derived DNA methylation (Illumina-HM450 methylation) for 454 Italian and 159 Dutch participants from the European Prospective Investigation into Cancer and Nutrition (EPIC). Long-term air pollution exposure levels, including NO2, NOx, PM2.5, PMcoarse, PM10, PM2.5 absorbance (soot) were estimated using models developed within the ESCAPE project, and back-extrapolated to the time of sampling when possible. We meta-analysed the associations between the air pollutants and global DNA methylation, methylation in functional regions and epigenome-wide methylation. CpG sites found differentially methylated with air pollution were further investigated for functional interpretation in an independent population (EnviroGenoMarkers project), where (N=613) participants had both methylation and gene expression data available. Exposure to NO2 was associated with a significant global somatic hypomethylation (p-value=0.014). Hypomethylation of CpG island's shores and shelves and gene bodies was significantly associated with higher exposures to NO2 and NOx. Meta-analysing the epigenome-wide findings of the 2 cohorts did not show genome-wide significant associations at single CpG site level. However, several significant CpG were found if the analyses were separated by countries. By regressing gene expression levels against methylation levels of the exposure-related CpG sites, we identified several significant CpG-transcript pairs and highlighted 5 enriched pathways for NO2 and 9 for NOx mainly related to the immune system and its regulation. Our findings support results on global hypomethylation associated with air pollution, and suggest that the shores and shelves of CpG islands and gene bodies are mostly affected by higher exposure to NO2 and NOx. Functional differences in the immune system were suggested by transcriptome analyses.
dc.language.isoenen
dc.rightsArchived with thanks to Environment internationalen
dc.titleDNA methylation and exposure to ambient air pollution in two prospective cohorts.en
dc.typeArticleen
dc.identifier.journalEnviron Int 2017, 108:127-36en
refterms.dateFOA2018-12-18T14:01:43Z
html.description.abstractLong-term exposure to air pollution has been associated with several adverse health effects including cardiovascular, respiratory diseases and cancers. However, underlying molecular alterations remain to be further investigated. The aim of this study is to investigate the effects of long-term exposure to air pollutants on (a) average DNA methylation at functional regions and, (b) individual differentially methylated CpG sites. An assumption is that omic measurements, including the methylome, are more sensitive to low doses than hard health outcomes. This study included blood-derived DNA methylation (Illumina-HM450 methylation) for 454 Italian and 159 Dutch participants from the European Prospective Investigation into Cancer and Nutrition (EPIC). Long-term air pollution exposure levels, including NO2, NOx, PM2.5, PMcoarse, PM10, PM2.5 absorbance (soot) were estimated using models developed within the ESCAPE project, and back-extrapolated to the time of sampling when possible. We meta-analysed the associations between the air pollutants and global DNA methylation, methylation in functional regions and epigenome-wide methylation. CpG sites found differentially methylated with air pollution were further investigated for functional interpretation in an independent population (EnviroGenoMarkers project), where (N=613) participants had both methylation and gene expression data available. Exposure to NO2 was associated with a significant global somatic hypomethylation (p-value=0.014). Hypomethylation of CpG island's shores and shelves and gene bodies was significantly associated with higher exposures to NO2 and NOx. Meta-analysing the epigenome-wide findings of the 2 cohorts did not show genome-wide significant associations at single CpG site level. However, several significant CpG were found if the analyses were separated by countries. By regressing gene expression levels against methylation levels of the exposure-related CpG sites, we identified several significant CpG-transcript pairs and highlighted 5 enriched pathways for NO2 and 9 for NOx mainly related to the immune system and its regulation. Our findings support results on global hypomethylation associated with air pollution, and suggest that the shores and shelves of CpG islands and gene bodies are mostly affected by higher exposure to NO2 and NOx. Functional differences in the immune system were suggested by transcriptome analyses.


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