Gaseous air pollutants and DNA methylation in a methylome-wide association study of an ethnically and environmentally diverse population of U.S. adults

Katelyn M. Holliday; Rahul Gondalia; Antoine Baldassari; Anne E. Justice; James D. Stewart; Duanping Liao; Jeff D. Yanosky; Kristina M. Jordahl; Parveen Bhatti; Themistocles L. Assimes; James S. Pankow; Weihua Guan; Myriam Fornage; Jan Bressler; Kari E. North; Karen N. Conneely; Yun Li; Lifang Hou; Pantel S. Vokonas; Cavin K. Ward-Caviness; Rory Wilson; Kathrin Wolf; Melanie Waldenberger; Josef Cyrys; Annette Peters; H. Marike Boezen; Judith M. Vonk; Sergi Sayols-Baixeras; Mikyeong Lee; Andrea A. Baccarelli; Eric A. Whitsel

doi:10.1016/j.envres.2022.113360

Gaseous air pollutants and DNA methylation in a methylome-wide association study of an ethnically and environmentally diverse population of U.S. adults

Katelyn M. Holliday, Rahul Gondalia, Antoine Baldassari, Anne E. Justice, James D. Stewart, Duanping Liao, Jeff D. Yanosky, Kristina M. Jordahl, Parveen Bhatti, Themistocles L. Assimes, James S. Pankow, Weihua Guan, Myriam Fornage, Jan Bressler, Kari E. North, Karen N. Conneely, Yun Li, Lifang Hou, Pantel S. Vokonas, Cavin K. Ward-CavinessRory Wilson, Kathrin Wolf, Melanie Waldenberger, Josef Cyrys, Annette Peters, H. Marike Boezen, Judith M. Vonk, Sergi Sayols-Baixeras, Mikyeong Lee, Andrea A. Baccarelli, Eric A. Whitsel

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Epigenetic mechanisms may underlie air pollution-health outcome associations. We estimated gaseous air pollutant-DNA methylation (DNAm) associations using twelve subpopulations within Women's Health Initiative (WHI) and Atherosclerosis Risk in Communities (ARIC) cohorts (n = 8397; mean age 61.3 years; 83% female; 46% African-American, 46% European-American, 8% Hispanic/Latino). We used geocoded participant address-specific mean ambient carbon monoxide (CO), nitrogen oxides (NO 2; NOx), ozone (O 3), and sulfur dioxide (SO 2) concentrations estimated over the 2-, 7-, 28-, and 365-day periods before collection of blood samples used to generate Illumina 450 k array leukocyte DNAm measurements. We estimated methylome-wide, subpopulation- and race/ethnicity-stratified pollutant-DNAm associations in multi-level, linear mixed-effects models adjusted for sociodemographic, behavioral, meteorological, and technical covariates. We combined stratum-specific estimates in inverse variance-weighted meta-analyses and characterized significant associations (false discovery rate; FDR<0.05) at Cytosine-phosphate-Guanine (CpG) sites without among-strata heterogeneity (P Cochran's Q > 0.05). We attempted replication in the Cooperative Health Research in Region of Augsburg (KORA) study and Normative Aging Study (NAS). We observed a -0.3 (95% CI: -0.4, -0.2) unit decrease in percent DNAm per interquartile range (IQR, 7.3 ppb) increase in 28-day mean NO 2 concentration at cg01885635 (chromosome 3; regulatory region 290 bp upstream from ZNF621; FDR = 0.03). At intragenic sites cg21849932 (chromosome 20; LIME1; intron 3) and cg05353869 (chromosome 11; KLHL35; exon 2), we observed a -0.3 (95% CI: -0.4, -0.2) unit decrease (FDR = 0.04) and a 1.2 (95% CI: 0.7, 1.7) unit increase (FDR = 0.04), respectively, in percent DNAm per IQR (17.6 ppb) increase in 7-day mean ozone concentration. Results were not fully replicated in KORA and NAS. We identified three CpG sites potentially susceptible to gaseous air pollution-induced DNAm changes near genes relevant for cardiovascular and lung disease. Further harmonized investigations with a range of gaseous pollutants and averaging durations are needed to determine the effect of gaseous air pollutants on DNA methylation and ultimately gene expression.

Original language	English (US)
Article number	113360
Journal	Environmental Research
Volume	212
Issue number	Pt C
DOIs	https://doi.org/10.1016/j.envres.2022.113360
State	Published - Sep 2022

Bibliographical note

Funding Information:
The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health , 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 , WHI-BAA23 by NHLBI 60,442,456 BAA23 , and WHI-EMPC by R01-ES020836 . The authors thank the WHI investigators and staff for their dedication and the study participants for making the program possible. A listing of WHI investigators can be found 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 .

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. ARIC DNAm funding was also provided by the American Recovery and Reinvestment Act of 2009 5RC2HL102419 and by R01-NS087541. 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 National Heart, Lung, and Blood Institute, National Institutes of Health, 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, WHI-BAA23 by NHLBI 60,442,456 BAA23, and WHI-EMPC by R01-ES020836. The authors thank the WHI investigators and staff for their dedication and the study participants for making the program possible. A listing of WHI investigators can be found 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. The KORA-Study Group consists of A. Peters (speaker), L. Schwettmann, R. Leidl, M. Heier, B. Linkohr, H. Grallert, C. Gieger, J. Linseisen, and their co-workers, who are responsible for the design and conduct of the KORA studies.NAS co-authors were supported by the National Institute of Environmental Health Sciences (grants ES000002, R01ES015172, 5R01ES027747-02, P30ES009089, R01ES021733, R01ES025225). The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center in Boston, MA.The Lifelines Epigenetics cohort was funded by consortium grant number 4.1.13.007 of the Lung foundation Netherlands. The Lifelines initiative has been made possible by funds from FES (Fonds Economische Structuurversterking), SNN (Samenwerkingsverband Noord Nederland) and REP (Ruimtelijk Economisch Programma).This project was also supported by NIEHS National Research Service Award T32-ES007018 and Building Interdisciplinary Research Careers in Women's Health K12HD043446 (KMH), NHLBI National Research Service Award T32-HL007055 (RG), NCI grant R25-CA094880 (KJ), NIEHS grant R01-ES017794 (EAW), NHGRI grant R01HG010297 (KEN), and the Basic Science Research Program, National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (2013R1A1A1057961) (ML). The authors declare they have no actual or potential competing financial interests.

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.

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. ARIC DNAm funding was also provided by the American Recovery and Reinvestment Act of 2009 5RC2HL102419 and by R01-NS087541. Data from the ARIC study are available on request at https://www2.cscc.unc.edu/aric/distribution-agreements .

Funding Information:
Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universität , as part of LMUinnovativ. The KORA-Study Group consists of A. Peters (speaker), L. Schwettmann, R. Leidl, M. Heier, B. Linkohr, H. Grallert, C. Gieger, J. Linseisen, and their co-workers, who are responsible for the design and conduct of the KORA studies.

Funding Information:
The Lifelines Epigenetics cohort was funded by consortium grant number 4.1.13.007 of the Lung foundation Netherlands. The Lifelines initiative has been made possible by funds from FES ( Fonds Economische Structuurversterking ), SNN ( Samenwerkingsverband Noord Nederland ) and REP ( Ruimtelijk Economisch Programma ).

Funding Information:
This project was also supported by NIEHS National Research Service Award T32-ES007018 and Building Interdisciplinary Research Careers in Women's Health K12HD043446 (KMH), NHLBI National Research Service Award T32-HL007055 (RG), NCI grant R25-CA094880 (KJ), NIEHS grant R01-ES017794 (EAW), NHGRI grant R01HG010297 (KEN), and the Basic Science Research Program, National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning ( 2013R1A1A1057961 ) (ML). The authors declare they have no actual or potential competing financial interests.

Funding Information:
NAS co-authors were supported by the National Institute of Environmental Health Sciences (grants ES000002 , R01ES015172 , 5R01ES027747-02, P30ES009089, R01ES021733, R01ES025225). The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center in Boston, MA.

Publisher Copyright:
© 2022 Elsevier Inc.

Keywords

Air pollution
DNA methylation
Epigenetics
Epigenome-wide association study
Gaseous pollutants
Nitrogen Dioxide/analysis
Humans
Middle Aged
Male
Air Pollution/analysis
DNA Methylation
Air Pollutants/analysis
Ozone/analysis
Adult
Female
Particulate Matter/analysis
Epigenome

PubMed: MeSH publication types

Research Support, Non-U.S. Gov't
Journal Article
Research Support, N.I.H., Extramural

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1016/j.envres.2022.113360

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Cite this

Holliday, K. M., Gondalia, R., Baldassari, A., Justice, A. E., Stewart, J. D., Liao, D., Yanosky, J. D., Jordahl, K. M., Bhatti, P., Assimes, T. L., Pankow, J. S., Guan, W., Fornage, M., Bressler, J., North, K. E., Conneely, K. N., Li, Y., Hou, L., Vokonas, P. S., ... Whitsel, E. A. (2022). Gaseous air pollutants and DNA methylation in a methylome-wide association study of an ethnically and environmentally diverse population of U.S. adults. Environmental Research, 212(Pt C), Article 113360. https://doi.org/10.1016/j.envres.2022.113360

Holliday, KM, Gondalia, R, Baldassari, A, Justice, AE, Stewart, JD, Liao, D, Yanosky, JD, Jordahl, KM, Bhatti, P, Assimes, TL, Pankow, JS , Guan, W, Fornage, M, Bressler, J, North, KE, Conneely, KN, Li, Y, Hou, L, Vokonas, PS, Ward-Caviness, CK, Wilson, R, Wolf, K, Waldenberger, M, Cyrys, J, Peters, A, Boezen, HM, Vonk, JM, Sayols-Baixeras, S, Lee, M, Baccarelli, AA & Whitsel, EA 2022, 'Gaseous air pollutants and DNA methylation in a methylome-wide association study of an ethnically and environmentally diverse population of U.S. adults', Environmental Research, vol. 212, no. Pt C, 113360. https://doi.org/10.1016/j.envres.2022.113360

@article{7a28a8d90be84e798ea82b2d0bbaae33,

title = "Gaseous air pollutants and DNA methylation in a methylome-wide association study of an ethnically and environmentally diverse population of U.S. adults",

abstract = "Epigenetic mechanisms may underlie air pollution-health outcome associations. We estimated gaseous air pollutant-DNA methylation (DNAm) associations using twelve subpopulations within Women's Health Initiative (WHI) and Atherosclerosis Risk in Communities (ARIC) cohorts (n = 8397; mean age 61.3 years; 83% female; 46% African-American, 46% European-American, 8% Hispanic/Latino). We used geocoded participant address-specific mean ambient carbon monoxide (CO), nitrogen oxides (NO 2; NOx), ozone (O 3), and sulfur dioxide (SO 2) concentrations estimated over the 2-, 7-, 28-, and 365-day periods before collection of blood samples used to generate Illumina 450 k array leukocyte DNAm measurements. We estimated methylome-wide, subpopulation- and race/ethnicity-stratified pollutant-DNAm associations in multi-level, linear mixed-effects models adjusted for sociodemographic, behavioral, meteorological, and technical covariates. We combined stratum-specific estimates in inverse variance-weighted meta-analyses and characterized significant associations (false discovery rate; FDR<0.05) at Cytosine-phosphate-Guanine (CpG) sites without among-strata heterogeneity (P Cochran's Q > 0.05). We attempted replication in the Cooperative Health Research in Region of Augsburg (KORA) study and Normative Aging Study (NAS). We observed a -0.3 (95% CI: -0.4, -0.2) unit decrease in percent DNAm per interquartile range (IQR, 7.3 ppb) increase in 28-day mean NO 2 concentration at cg01885635 (chromosome 3; regulatory region 290 bp upstream from ZNF621; FDR = 0.03). At intragenic sites cg21849932 (chromosome 20; LIME1; intron 3) and cg05353869 (chromosome 11; KLHL35; exon 2), we observed a -0.3 (95% CI: -0.4, -0.2) unit decrease (FDR = 0.04) and a 1.2 (95% CI: 0.7, 1.7) unit increase (FDR = 0.04), respectively, in percent DNAm per IQR (17.6 ppb) increase in 7-day mean ozone concentration. Results were not fully replicated in KORA and NAS. We identified three CpG sites potentially susceptible to gaseous air pollution-induced DNAm changes near genes relevant for cardiovascular and lung disease. Further harmonized investigations with a range of gaseous pollutants and averaging durations are needed to determine the effect of gaseous air pollutants on DNA methylation and ultimately gene expression. ",

keywords = "Air pollution, DNA methylation, Epigenetics, Epigenome-wide association study, Gaseous pollutants, Nitrogen Dioxide/analysis, Humans, Middle Aged, Male, Air Pollution/analysis, DNA Methylation, Air Pollutants/analysis, Ozone/analysis, Adult, Female, Particulate Matter/analysis, Epigenome",

author = "Holliday, {Katelyn M.} and Rahul Gondalia and Antoine Baldassari and Justice, {Anne E.} and Stewart, {James D.} and Duanping Liao and Yanosky, {Jeff D.} and Jordahl, {Kristina M.} and Parveen Bhatti and Assimes, {Themistocles L.} and Pankow, {James S.} and Weihua Guan and Myriam Fornage and Jan Bressler and North, {Kari E.} and Conneely, {Karen N.} and Yun Li and Lifang Hou and Vokonas, {Pantel S.} and Ward-Caviness, {Cavin K.} and Rory Wilson and Kathrin Wolf and Melanie Waldenberger and Josef Cyrys and Annette Peters and Boezen, {H. Marike} and Vonk, {Judith M.} and Sergi Sayols-Baixeras and Mikyeong Lee and Baccarelli, {Andrea A.} and Whitsel, {Eric A.}",

note = "Funding Information: The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health , 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 , WHI-BAA23 by NHLBI 60,442,456 BAA23 , and WHI-EMPC by R01-ES020836 . The authors thank the WHI investigators and staff for their dedication and the study participants for making the program possible. A listing of WHI investigators can be found 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 . 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. ARIC DNAm funding was also provided by the American Recovery and Reinvestment Act of 2009 5RC2HL102419 and by R01-NS087541. 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 National Heart, Lung, and Blood Institute, National Institutes of Health, 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, WHI-BAA23 by NHLBI 60,442,456 BAA23, and WHI-EMPC by R01-ES020836. The authors thank the WHI investigators and staff for their dedication and the study participants for making the program possible. A listing of WHI investigators can be found 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. The KORA-Study Group consists of A. Peters (speaker), L. Schwettmann, R. Leidl, M. Heier, B. Linkohr, H. Grallert, C. Gieger, J. Linseisen, and their co-workers, who are responsible for the design and conduct of the KORA studies.NAS co-authors were supported by the National Institute of Environmental Health Sciences (grants ES000002, R01ES015172, 5R01ES027747-02, P30ES009089, R01ES021733, R01ES025225). The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center in Boston, MA.The Lifelines Epigenetics cohort was funded by consortium grant number 4.1.13.007 of the Lung foundation Netherlands. The Lifelines initiative has been made possible by funds from FES (Fonds Economische Structuurversterking), SNN (Samenwerkingsverband Noord Nederland) and REP (Ruimtelijk Economisch Programma).This project was also supported by NIEHS National Research Service Award T32-ES007018 and Building Interdisciplinary Research Careers in Women's Health K12HD043446 (KMH), NHLBI National Research Service Award T32-HL007055 (RG), NCI grant R25-CA094880 (KJ), NIEHS grant R01-ES017794 (EAW), NHGRI grant R01HG010297 (KEN), and the Basic Science Research Program, National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (2013R1A1A1057961) (ML). The authors declare they have no actual or potential competing financial interests. Funding Information: The KORA study was initiated and financed by the Helmholtz Zentrum M{\"u}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. 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. ARIC DNAm funding was also provided by the American Recovery and Reinvestment Act of 2009 5RC2HL102419 and by R01-NS087541. Data from the ARIC study are available on request at https://www2.cscc.unc.edu/aric/distribution-agreements . Funding Information: Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universit{\"a}t , as part of LMUinnovativ. The KORA-Study Group consists of A. Peters (speaker), L. Schwettmann, R. Leidl, M. Heier, B. Linkohr, H. Grallert, C. Gieger, J. Linseisen, and their co-workers, who are responsible for the design and conduct of the KORA studies. Funding Information: The Lifelines Epigenetics cohort was funded by consortium grant number 4.1.13.007 of the Lung foundation Netherlands. The Lifelines initiative has been made possible by funds from FES ( Fonds Economische Structuurversterking ), SNN ( Samenwerkingsverband Noord Nederland ) and REP ( Ruimtelijk Economisch Programma ). Funding Information: This project was also supported by NIEHS National Research Service Award T32-ES007018 and Building Interdisciplinary Research Careers in Women's Health K12HD043446 (KMH), NHLBI National Research Service Award T32-HL007055 (RG), NCI grant R25-CA094880 (KJ), NIEHS grant R01-ES017794 (EAW), NHGRI grant R01HG010297 (KEN), and the Basic Science Research Program, National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning ( 2013R1A1A1057961 ) (ML). The authors declare they have no actual or potential competing financial interests. Funding Information: NAS co-authors were supported by the National Institute of Environmental Health Sciences (grants ES000002 , R01ES015172 , 5R01ES027747-02, P30ES009089, R01ES021733, R01ES025225). The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center in Boston, MA. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",

year = "2022",

month = sep,

doi = "10.1016/j.envres.2022.113360",

language = "English (US)",

volume = "212",

journal = "Environmental Research",

issn = "0013-9351",

publisher = "Academic Press Inc.",

number = "Pt C",

}

TY - JOUR

T1 - Gaseous air pollutants and DNA methylation in a methylome-wide association study of an ethnically and environmentally diverse population of U.S. adults

AU - Holliday, Katelyn M.

AU - Gondalia, Rahul

AU - Baldassari, Antoine

AU - Justice, Anne E.

AU - Stewart, James D.

AU - Liao, Duanping

AU - Yanosky, Jeff D.

AU - Jordahl, Kristina M.

AU - Bhatti, Parveen

AU - Assimes, Themistocles L.

AU - Pankow, James S.

AU - Guan, Weihua

AU - Fornage, Myriam

AU - Bressler, Jan

AU - North, Kari E.

AU - Conneely, Karen N.

AU - Li, Yun

AU - Hou, Lifang

AU - Vokonas, Pantel S.

AU - Ward-Caviness, Cavin K.

AU - Wilson, Rory

AU - Wolf, Kathrin

AU - Waldenberger, Melanie

AU - Cyrys, Josef

AU - Peters, Annette

AU - Boezen, H. Marike

AU - Vonk, Judith M.

AU - Sayols-Baixeras, Sergi

AU - Lee, Mikyeong

AU - Baccarelli, Andrea A.

AU - Whitsel, Eric A.

N1 - Funding Information: The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health , 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 , WHI-BAA23 by NHLBI 60,442,456 BAA23 , and WHI-EMPC by R01-ES020836 . The authors thank the WHI investigators and staff for their dedication and the study participants for making the program possible. A listing of WHI investigators can be found 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 . 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. ARIC DNAm funding was also provided by the American Recovery and Reinvestment Act of 2009 5RC2HL102419 and by R01-NS087541. 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 National Heart, Lung, and Blood Institute, National Institutes of Health, 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, WHI-BAA23 by NHLBI 60,442,456 BAA23, and WHI-EMPC by R01-ES020836. The authors thank the WHI investigators and staff for their dedication and the study participants for making the program possible. A listing of WHI investigators can be found 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. The KORA-Study Group consists of A. Peters (speaker), L. Schwettmann, R. Leidl, M. Heier, B. Linkohr, H. Grallert, C. Gieger, J. Linseisen, and their co-workers, who are responsible for the design and conduct of the KORA studies.NAS co-authors were supported by the National Institute of Environmental Health Sciences (grants ES000002, R01ES015172, 5R01ES027747-02, P30ES009089, R01ES021733, R01ES025225). The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center in Boston, MA.The Lifelines Epigenetics cohort was funded by consortium grant number 4.1.13.007 of the Lung foundation Netherlands. The Lifelines initiative has been made possible by funds from FES (Fonds Economische Structuurversterking), SNN (Samenwerkingsverband Noord Nederland) and REP (Ruimtelijk Economisch Programma).This project was also supported by NIEHS National Research Service Award T32-ES007018 and Building Interdisciplinary Research Careers in Women's Health K12HD043446 (KMH), NHLBI National Research Service Award T32-HL007055 (RG), NCI grant R25-CA094880 (KJ), NIEHS grant R01-ES017794 (EAW), NHGRI grant R01HG010297 (KEN), and the Basic Science Research Program, National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (2013R1A1A1057961) (ML). The authors declare they have no actual or potential competing financial interests. 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. 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. ARIC DNAm funding was also provided by the American Recovery and Reinvestment Act of 2009 5RC2HL102419 and by R01-NS087541. Data from the ARIC study are available on request at https://www2.cscc.unc.edu/aric/distribution-agreements . Funding Information: Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universität , as part of LMUinnovativ. The KORA-Study Group consists of A. Peters (speaker), L. Schwettmann, R. Leidl, M. Heier, B. Linkohr, H. Grallert, C. Gieger, J. Linseisen, and their co-workers, who are responsible for the design and conduct of the KORA studies. Funding Information: The Lifelines Epigenetics cohort was funded by consortium grant number 4.1.13.007 of the Lung foundation Netherlands. The Lifelines initiative has been made possible by funds from FES ( Fonds Economische Structuurversterking ), SNN ( Samenwerkingsverband Noord Nederland ) and REP ( Ruimtelijk Economisch Programma ). Funding Information: This project was also supported by NIEHS National Research Service Award T32-ES007018 and Building Interdisciplinary Research Careers in Women's Health K12HD043446 (KMH), NHLBI National Research Service Award T32-HL007055 (RG), NCI grant R25-CA094880 (KJ), NIEHS grant R01-ES017794 (EAW), NHGRI grant R01HG010297 (KEN), and the Basic Science Research Program, National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning ( 2013R1A1A1057961 ) (ML). The authors declare they have no actual or potential competing financial interests. Funding Information: NAS co-authors were supported by the National Institute of Environmental Health Sciences (grants ES000002 , R01ES015172 , 5R01ES027747-02, P30ES009089, R01ES021733, R01ES025225). The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center in Boston, MA. Publisher Copyright: © 2022 Elsevier Inc.

PY - 2022/9

Y1 - 2022/9

N2 - Epigenetic mechanisms may underlie air pollution-health outcome associations. We estimated gaseous air pollutant-DNA methylation (DNAm) associations using twelve subpopulations within Women's Health Initiative (WHI) and Atherosclerosis Risk in Communities (ARIC) cohorts (n = 8397; mean age 61.3 years; 83% female; 46% African-American, 46% European-American, 8% Hispanic/Latino). We used geocoded participant address-specific mean ambient carbon monoxide (CO), nitrogen oxides (NO 2; NOx), ozone (O 3), and sulfur dioxide (SO 2) concentrations estimated over the 2-, 7-, 28-, and 365-day periods before collection of blood samples used to generate Illumina 450 k array leukocyte DNAm measurements. We estimated methylome-wide, subpopulation- and race/ethnicity-stratified pollutant-DNAm associations in multi-level, linear mixed-effects models adjusted for sociodemographic, behavioral, meteorological, and technical covariates. We combined stratum-specific estimates in inverse variance-weighted meta-analyses and characterized significant associations (false discovery rate; FDR<0.05) at Cytosine-phosphate-Guanine (CpG) sites without among-strata heterogeneity (P Cochran's Q > 0.05). We attempted replication in the Cooperative Health Research in Region of Augsburg (KORA) study and Normative Aging Study (NAS). We observed a -0.3 (95% CI: -0.4, -0.2) unit decrease in percent DNAm per interquartile range (IQR, 7.3 ppb) increase in 28-day mean NO 2 concentration at cg01885635 (chromosome 3; regulatory region 290 bp upstream from ZNF621; FDR = 0.03). At intragenic sites cg21849932 (chromosome 20; LIME1; intron 3) and cg05353869 (chromosome 11; KLHL35; exon 2), we observed a -0.3 (95% CI: -0.4, -0.2) unit decrease (FDR = 0.04) and a 1.2 (95% CI: 0.7, 1.7) unit increase (FDR = 0.04), respectively, in percent DNAm per IQR (17.6 ppb) increase in 7-day mean ozone concentration. Results were not fully replicated in KORA and NAS. We identified three CpG sites potentially susceptible to gaseous air pollution-induced DNAm changes near genes relevant for cardiovascular and lung disease. Further harmonized investigations with a range of gaseous pollutants and averaging durations are needed to determine the effect of gaseous air pollutants on DNA methylation and ultimately gene expression.

AB - Epigenetic mechanisms may underlie air pollution-health outcome associations. We estimated gaseous air pollutant-DNA methylation (DNAm) associations using twelve subpopulations within Women's Health Initiative (WHI) and Atherosclerosis Risk in Communities (ARIC) cohorts (n = 8397; mean age 61.3 years; 83% female; 46% African-American, 46% European-American, 8% Hispanic/Latino). We used geocoded participant address-specific mean ambient carbon monoxide (CO), nitrogen oxides (NO 2; NOx), ozone (O 3), and sulfur dioxide (SO 2) concentrations estimated over the 2-, 7-, 28-, and 365-day periods before collection of blood samples used to generate Illumina 450 k array leukocyte DNAm measurements. We estimated methylome-wide, subpopulation- and race/ethnicity-stratified pollutant-DNAm associations in multi-level, linear mixed-effects models adjusted for sociodemographic, behavioral, meteorological, and technical covariates. We combined stratum-specific estimates in inverse variance-weighted meta-analyses and characterized significant associations (false discovery rate; FDR<0.05) at Cytosine-phosphate-Guanine (CpG) sites without among-strata heterogeneity (P Cochran's Q > 0.05). We attempted replication in the Cooperative Health Research in Region of Augsburg (KORA) study and Normative Aging Study (NAS). We observed a -0.3 (95% CI: -0.4, -0.2) unit decrease in percent DNAm per interquartile range (IQR, 7.3 ppb) increase in 28-day mean NO 2 concentration at cg01885635 (chromosome 3; regulatory region 290 bp upstream from ZNF621; FDR = 0.03). At intragenic sites cg21849932 (chromosome 20; LIME1; intron 3) and cg05353869 (chromosome 11; KLHL35; exon 2), we observed a -0.3 (95% CI: -0.4, -0.2) unit decrease (FDR = 0.04) and a 1.2 (95% CI: 0.7, 1.7) unit increase (FDR = 0.04), respectively, in percent DNAm per IQR (17.6 ppb) increase in 7-day mean ozone concentration. Results were not fully replicated in KORA and NAS. We identified three CpG sites potentially susceptible to gaseous air pollution-induced DNAm changes near genes relevant for cardiovascular and lung disease. Further harmonized investigations with a range of gaseous pollutants and averaging durations are needed to determine the effect of gaseous air pollutants on DNA methylation and ultimately gene expression.

KW - Air pollution

KW - DNA methylation

KW - Epigenetics

KW - Epigenome-wide association study

KW - Gaseous pollutants

KW - Nitrogen Dioxide/analysis

KW - Humans

KW - Middle Aged

KW - Male

KW - Air Pollution/analysis

KW - DNA Methylation

KW - Air Pollutants/analysis

KW - Ozone/analysis

KW - Adult

KW - Female

KW - Particulate Matter/analysis

KW - Epigenome

UR - http://www.scopus.com/inward/record.url?scp=85129465479&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85129465479&partnerID=8YFLogxK

U2 - 10.1016/j.envres.2022.113360

DO - 10.1016/j.envres.2022.113360

M3 - Article

C2 - 35500859

AN - SCOPUS:85129465479

SN - 0013-9351

VL - 212

JO - Environmental Research

JF - Environmental Research

IS - Pt C

M1 - 113360

ER -

Gaseous air pollutants and DNA methylation in a methylome-wide association study of an ethnically and environmentally diverse population of U.S. adults

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