Methylome-wide association study provides evidence of particulate matter air pollution-associated DNA methylation

Rahul Gondalia, Antoine Baldassari, Katelyn M. Holliday, Anne E. Justice, Raúl Méndez-Giráldez, James D. Stewart, Duanping Liao, Jeff D. Yanosky, Kasey J.M. Brennan, Stephanie M. Engel, Kristina M. Jordahl, Elizabeth Kennedy, Cavin K. Ward-Caviness, Kathrin Wolf, Melanie Waldenberger, Josef Cyrys, Annette Peters, Parveen Bhatti, Steve Horvath, Themistocles L. AssimesJames S. Pankow, Ellen W. Demerath, Weihua Guan, Myriam Fornage, Jan Bressler, Kari E. North, Karen N. Conneely, Yun Li, Lifang Hou, Andrea A. Baccarelli, Eric A. Whitsel

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Article number104723
JournalEnvironment International
Volume132
DOIs
StatePublished - Nov 2019

Bibliographical note

Funding Information:
The KORA study was initiated and financed by the Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universität, as part of LMUinnovativ.

Funding Information:
This work was supported by NIEHS grant R01-ES020836 (LH, AB, EAW), NHLBI contract HHSN268201100046C (KC), NIEHS grant R01-ES017794 (EAW), NHLBI National Research Service Award T32-HL007055 (RG), NIEHS National Research Service Award T32-ES007018 (KH), and NCI grant R25-CA094880 (KJ).

Funding Information:
The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract numbers HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I and HHSN268201700005I). The authors thank the staff and participants of the ARIC study for their important contributions. Funding was also supported by 5RC2HL102419 and R01NS087541. Data from the ARIC study are available on request at https://www2.cscc.unc.edu/aric/distribution-agreements. The WHI program is funded by the NHLBI, U.S. Department of Health and Human Services, through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. WHI-AS311 was supported by American Cancer Society award 125299-RSG-13-100-01-CCE. All contributors to WHI science are listed at https://www.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Long%20List.pdf. Data from the WHI are available on request at https://www.whi.org/researchers/SitePages/Write%20a%20Paper.aspx. The KORA study was initiated and financed by the Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universität, as part of LMUinnovativ. This work was supported by NIEHS grant R01-ES020836 (LH, AB, EAW), NHLBI contract HHSN268201100046C (KC), NIEHS grant R01-ES017794 (EAW), NHLBI National Research Service Award T32-HL007055 (RG), NIEHS National Research Service Award T32-ES007018 (KH), and NCI grant R25-CA094880 (KJ). No authors have declared a potential conflicts of interest.

Funding Information:
The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract numbers HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I and HHSN268201700005I). The authors thank the staff and participants of the ARIC study for their important contributions. Funding was also supported by 5RC2HL102419 and R01NS087541. Data from the ARIC study are available on request at https://www2.cscc.unc.edu/aric/distribution-agreements .

Funding Information:
The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract numbers HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I and HHSN268201700005I). The authors thank the staff and participants of the ARIC study for their important contributions. Funding was also supported by 5RC2HL102419 and R01NS087541. Data from the ARIC study are available on request at https://www2.cscc.unc.edu/aric/distribution-agreements. The WHI program is funded by the NHLBI, U.S. Department of Health and Human Services, through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. WHI-AS311 was supported by American Cancer Society award 125299-RSG-13-100-01-CCE. All contributors to WHI science are listed at https://www.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Long%20List.pdf. Data from the WHI are available on request at https://www.whi.org/researchers/SitePages/Write%20a%20Paper.aspx. The KORA study was initiated and financed by the Helmholtz Zentrum M?nchen ? German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universit?t, as part of LMUinnovativ. This work was supported by NIEHS grant R01-ES020836 (LH, AB, EAW), NHLBI contract HHSN268201100046C (KC), NIEHS grant R01-ES017794 (EAW), NHLBI National Research Service Award T32-HL007055 (RG), NIEHS National Research Service Award T32-ES007018 (KH), and NCI grant R25-CA094880 (KJ). No authors have declared a potential conflicts of interest.

Funding Information:
The WHI program is funded by the NHLBI, U.S. Department of Health and Human Services, through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. WHI-AS311 was supported by American Cancer Society award 125299-RSG-13-100-01-CCE. All contributors to WHI science are listed at https://www.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Long%20List.pdf . Data from the WHI are available on request at https://www.whi.org/researchers/SitePages/Write%20a%20Paper.aspx .

Publisher Copyright:
© 2019 The Authors

Keywords

  • Air pollution
  • DNA methylation
  • Epigenetics
  • Epigenome-wide association study
  • Particulate matter

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