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Wildfire-related PM2.5 and DNA methylation: An Australian twin and family study
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Highlights Wildfire PM2.5 was associated with DNA methylation of many human genome loci. Those loci were mapped to 47 genes related to many human diseases. The genes were enriched in inflammatory regulation and platelet activation pathways. DNA methylation signatures of wildfire and non-wildfire PM2.5 were quite different.
Abstract Background Wildfire-related fine particulate matter (PM2.5) has many adverse health impacts, but its impacts on human epigenome are unknown. We aimed to evaluate the associations between long-term exposure to wildfire-related PM2.5 and blood DNA methylation, and whether the associations differ from those with non-wildfire-related PM2.5. Methods We studied 479 Australian women comprising 132 twin pairs and 215 of their sisters. Blood-derived DNA methylation was measured using the HumanMethylation450 BeadChip array. Data on 3-year (year of blood collection and previous two years) average wildfire-related and non-wildfire-related PM2.5 at 0.01°×0.01° spatial resolution were created by combining information from satellite observations, chemical transport models, and ground-based observations. Exposure data were linked to each participant’s home address, assuming the address did not change during the exposure window. For DNA methylation of each cytosine-guanine dinucleotide (CpG), and for global DNA methylation represented by the average of all measured CpGs or CpGs in repetitive elements, we evaluated their associations with wildfire- or non-wildfire-related PM2.5 using a within-sibship analysis controlling for factors shared between siblings and other important covariates. Differentially methylated regions (DMRs) were defined by comb-p and DMRcate. Results The 3-year average wildfire-related PM2.5 (range: 0.3 to 7.6 µg/m3 , mean: 1.6 µg/m3) was negatively, but not significantly (p-values greater than 0.05) associated with all seven global DNA methylation measures. There were 26 CpGs and 33 DMRs associated with wildfire-related PM2.5 (Bonferroni adjusted p-value < 0.05) mapped to 47 genes enriched for pathways related to inflammatory regulation and platelet activation. These genes have been related to many human diseases or phenotypes e.g., cancer, mental disorders, diabetes, obesity, asthma, blood pressure. These CpGs, DMRs and enriched pathways did not overlap with the 1 CpG and 7 DMRs associated with non-wildfire-related PM2.5. Conclusions Long-term exposure to wildfire-related PM2.5 was associated with various blood DNA methylation signatures in Australian women, and these were distinct from those associated with non-wildfire-related PM2.5.
Wildfire-related PM2.5 and DNA methylation: An Australian twin and family study
Graphical abstract Display Omitted
Highlights Wildfire PM2.5 was associated with DNA methylation of many human genome loci. Those loci were mapped to 47 genes related to many human diseases. The genes were enriched in inflammatory regulation and platelet activation pathways. DNA methylation signatures of wildfire and non-wildfire PM2.5 were quite different.
Abstract Background Wildfire-related fine particulate matter (PM2.5) has many adverse health impacts, but its impacts on human epigenome are unknown. We aimed to evaluate the associations between long-term exposure to wildfire-related PM2.5 and blood DNA methylation, and whether the associations differ from those with non-wildfire-related PM2.5. Methods We studied 479 Australian women comprising 132 twin pairs and 215 of their sisters. Blood-derived DNA methylation was measured using the HumanMethylation450 BeadChip array. Data on 3-year (year of blood collection and previous two years) average wildfire-related and non-wildfire-related PM2.5 at 0.01°×0.01° spatial resolution were created by combining information from satellite observations, chemical transport models, and ground-based observations. Exposure data were linked to each participant’s home address, assuming the address did not change during the exposure window. For DNA methylation of each cytosine-guanine dinucleotide (CpG), and for global DNA methylation represented by the average of all measured CpGs or CpGs in repetitive elements, we evaluated their associations with wildfire- or non-wildfire-related PM2.5 using a within-sibship analysis controlling for factors shared between siblings and other important covariates. Differentially methylated regions (DMRs) were defined by comb-p and DMRcate. Results The 3-year average wildfire-related PM2.5 (range: 0.3 to 7.6 µg/m3 , mean: 1.6 µg/m3) was negatively, but not significantly (p-values greater than 0.05) associated with all seven global DNA methylation measures. There were 26 CpGs and 33 DMRs associated with wildfire-related PM2.5 (Bonferroni adjusted p-value < 0.05) mapped to 47 genes enriched for pathways related to inflammatory regulation and platelet activation. These genes have been related to many human diseases or phenotypes e.g., cancer, mental disorders, diabetes, obesity, asthma, blood pressure. These CpGs, DMRs and enriched pathways did not overlap with the 1 CpG and 7 DMRs associated with non-wildfire-related PM2.5. Conclusions Long-term exposure to wildfire-related PM2.5 was associated with various blood DNA methylation signatures in Australian women, and these were distinct from those associated with non-wildfire-related PM2.5.
Wildfire-related PM2.5 and DNA methylation: An Australian twin and family study
Xu, Rongbin (author) / Li, Shanshan (author) / Wu, Yao (author) / Yue, Xu (author) / Wong, Ee Ming (author) / Southey, Melissa C. (author) / Hopper, John L. (author) / Abramson, Michael J. (author) / Li, Shuai (author) / Guo, Yuming (author)
2022-12-16
Article (Journal)
Electronic Resource
English
PM<inf>2.5</inf> , Wildfire smoke , DNA methylation , Epigenome-wide association study , Twin and family study , Alu , <italic>Arthrobacter luteus</italic> , AMDTSS , Australian Mammographic Density Twins and Sisters Study , BIF , Bayesian inflation factors , CpG , cytosine-guanine dinucleotide , DMR , differentially methylated region , FDR , false discovery rate , GEE , generalized estimating equation , GO , Gene Ontology , IRSAD , Index of Relative Socioeconomic Advantage and Disadvantage , KEGG , Kyoto Encyclopedia of Genes and Genomes , L1 , long interspersed elements 1 , LTR , long terminal repeat , PM2.5 , particulate matter with a diameter of 2.5 micrometres or less , REs , repetitive elements , SES , socioeconomic status
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