Short- and intermediate-term exposure to ambient fine particulate elements and leukocyte epigenome-wide DNA methylation in older men: the Normative Aging Study

doi:10.1016/j.envint.2021.106955

. 2022 Jan:158:106955.

doi: 10.1016/j.envint.2021.106955. Epub 2021 Oct 28.

Short- and intermediate-term exposure to ambient fine particulate elements and leukocyte epigenome-wide DNA methylation in older men: the Normative Aging Study

Affiliations

¹ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. Electronic address: cuicuiwang@hsph.harvard.edu.
² Division of Environmental Health Sciences, School of Public Health and Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
³ Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
⁴ Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁵ Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
⁶ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
⁷ Department of Environmental Health Sciences, Columbia Mailman School of Public Health, New York, NY 10032, USA.
⁸ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.

PMID: 34717175
PMCID: PMC8710082
DOI: 10.1016/j.envint.2021.106955

Short- and intermediate-term exposure to ambient fine particulate elements and leukocyte epigenome-wide DNA methylation in older men: the Normative Aging Study

Cuicui Wang et al. Environ Int. 2022 Jan.

. 2022 Jan:158:106955.

doi: 10.1016/j.envint.2021.106955. Epub 2021 Oct 28.

Authors

Affiliations

¹ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. Electronic address: cuicuiwang@hsph.harvard.edu.
² Division of Environmental Health Sciences, School of Public Health and Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
³ Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
⁴ Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁵ Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
⁶ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
⁷ Department of Environmental Health Sciences, Columbia Mailman School of Public Health, New York, NY 10032, USA.
⁸ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.

PMID: 34717175
PMCID: PMC8710082
DOI: 10.1016/j.envint.2021.106955

Abstract

Background: Several epigenome-wide association studies (EWAS) of ambient particulate matter with aerodynamic diameter ≤ 2.5 µm (PM_2.5) have been reported. However, EWAS of PM_2.5 elements (PEs), reflecting different emission sources, are very limited.

Objectives: We performed EWAS of short- and intermediate-term exposure to PM_2.5 and 13 PEs. We hypothesized that significant changes in DNAm may vary by PM_2.5 mass and its elements.

Methods: We repeatedly collected blood samples in the Normative Aging Study and measured leukocyte DNA methylation (DNAm) with the Illumina HumanMethylation450K BeadChip. We collected daily PM_2.5 and 13 PEs at a fixed central site. To estimate the associations between each PE and DNAm at individual cytosine-phosphate-guanine (CpG) sites, we incorporated a distributed-lag (0-27 d) term in the setting of median regression with subject-specific intercept and examined cumulative lag associations. We also accounted for selection bias due to loss to follow-up and mortality prior to enrollment. Significantly differentially methylated probes (DMPs) were identified using Bonferroni correction for multiple testing. We further conducted regional and pathway analyses to identify significantly differentially methylated regions (DMRs) and pathways.

Results: We included 695 men with 1,266 visits between 1999 and 2013. The subjects had a mean age of 75 years. The significant DMPs, DMRs, and pathways varied by to PM_2.5 total mass and PEs. For example, PM_2.5 total mass was associated with 2,717 DMPs and 10,470 DMRs whereas Pb was associated with 3,173 DMPs and 637 DMRs. The identified pathways by PM_2.5 mass were mostly involved in mood disorders, neuroplasticity, immunity, and inflammation, whereas the pathways associated with motor vehicles (BC, Cu, Pb, and Zn) were related with cardiovascular disease and cancer (e.g., "PPARs signaling").

Conclusions: PM_2.5 and PE were associated with methylation changes at multiple probes and along multiple pathways, in ways that varied by particle components.

Keywords: DNA methylation; Distributed-lag; Epigenome-wide association study; PM(2.5); PM(2.5) elements; Pathway analyses.

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Conflict of interest statement

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

**Fig. 1.**
The heatmap of 53 differentially methylated probes that were associated with both PM_2.5 mass and at least one of its 13 PEs. Abbreviations: PM_2.5, particulate matter with an aerodynamic diameter ≤ 2.5 µm; BC, black carbon; Cu, copper; Pb, lead; Zn, zinc; Ni, nickel; V, vanadium; Ca, calcium; Fe, iron; Al, aluminum; Si, silicon; K, potassium; S, sulfur; Na, sodium.

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References

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[1] BeadArray controls reporter, 2015. San Diego, CA: Illumina; October1000000004009v00.

[2] BeadArray controls reporter, 2015. San Diego, CA: Illumina; October1000000004009v00.

[3] Amare AT, Schubert KO, Klingler-Hoffmann M, Cohen-Woods S, Baune BT, 2017. The genetic overlap between mood disorders and cardiometabolic diseases: a systematic review of genome wide and candidate gene studies. e1007 e1007 Transl. Psychiatry 7 (1). 10.1038/tp.2016.261. - DOI - PMC - PubMed

[4] Amare AT, Schubert KO, Klingler-Hoffmann M, Cohen-Woods S, Baune BT, 2017. The genetic overlap between mood disorders and cardiometabolic diseases: a systematic review of genome wide and candidate gene studies. e1007 e1007 Transl. Psychiatry 7 (1). 10.1038/tp.2016.261. - DOI - PMC - PubMed

[5] Baccarelli A, Wright RO, Bollati V, Tarantini L, Litonjua AA, Suh HH, Zanobetti A, Sparrow D, Vokonas PS, Schwartz J, 2009. Rapid DNA methylation changes after exposure to traffic particles. Am. J. Respir. Crit. Care Med 179 (7), 572–578. 10.1164/rccm.200807-1097OC. - DOI - PMC - PubMed

[6] Baccarelli A, Wright RO, Bollati V, Tarantini L, Litonjua AA, Suh HH, Zanobetti A, Sparrow D, Vokonas PS, Schwartz J, 2009. Rapid DNA methylation changes after exposure to traffic particles. Am. J. Respir. Crit. Care Med 179 (7), 572–578. 10.1164/rccm.200807-1097OC. - DOI - PMC - PubMed

[7] Bell B, Rose CL, Damon A, 1966. The Veterans Administration longitudinal study of healthy aging. Gerontologist 6 (4), 179–184. 10.1093/geront/6.4.179. - DOI - PubMed

[8] Bell B, Rose CL, Damon A, 1966. The Veterans Administration longitudinal study of healthy aging. Gerontologist 6 (4), 179–184. 10.1093/geront/6.4.179. - DOI - PubMed

[9] Bind M-A, Coull BA, Baccarelli A, Tarantini L, Cantone L, Vokonas P, Schwartz J, 2016. Distributional changes in gene-specific methylation associated with temperature. Environ. Res 150, 38–46. 10.1016/j.envres.2016.05.034. - DOI - PMC - PubMed

[10] Bind M-A, Coull BA, Baccarelli A, Tarantini L, Cantone L, Vokonas P, Schwartz J, 2016. Distributional changes in gene-specific methylation associated with temperature. Environ. Res 150, 38–46. 10.1016/j.envres.2016.05.034. - DOI - PMC - PubMed

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Short- and intermediate-term exposure to ambient fine particulate elements and leukocyte epigenome-wide DNA methylation in older men: the Normative Aging Study

Affiliations

Short- and intermediate-term exposure to ambient fine particulate elements and leukocyte epigenome-wide DNA methylation in older men: the Normative Aging Study

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Abstract

Conflict of interest statement

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