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

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)

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

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methylation
particulate matter
atmospheric pollution
DNA
subpopulation
chromosome
phosphate
genomics
blood
womens health
African American
cardiovascular disease
ethnicity
gene expression
gene

Keywords

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

ASJC Scopus subject areas

  • Environmental Science(all)

Cite this

Gondalia, R., Baldassari, A., Holliday, K. M., Justice, A. E., Méndez-Giráldez, R., Stewart, J. D., ... Whitsel, E. A. (2019). Methylome-wide association study provides evidence of particulate matter air pollution-associated DNA methylation. Environment International, 132, [104723]. https://doi.org/10.1016/j.envint.2019.03.071
Gondalia, Rahul ; Baldassari, Antoine ; Holliday, Katelyn M. ; Justice, Anne E. ; Méndez-Giráldez, Raúl ; Stewart, James D. ; Liao, Duanping ; Yanosky, Jeff D. ; Brennan, Kasey J.M. ; Engel, Stephanie M. ; Jordahl, Kristina M. ; Kennedy, Elizabeth ; Ward-Caviness, Cavin K. ; Wolf, Kathrin ; Waldenberger, Melanie ; Cyrys, Josef ; Peters, Annette ; Bhatti, Parveen ; Horvath, Steve ; Assimes, Themistocles L. ; Pankow, James S. ; Demerath, Ellen W. ; Guan, Weihua ; Fornage, Myriam ; Bressler, Jan ; North, Kari E. ; Conneely, Karen N. ; Li, Yun ; Hou, Lifang ; Baccarelli, Andrea A. ; Whitsel, Eric A. / Methylome-wide association study provides evidence of particulate matter air pollution-associated DNA methylation. In: Environment International. 2019 ; Vol. 132.
@article{382de40334f14a7da553a42d39952f53,
title = "Methylome-wide association study provides evidence of particulate matter air pollution-associated DNA methylation",
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.",
keywords = "Air pollution, DNA methylation, Epigenetics, Epigenome-wide association study, Particulate matter",
author = "Rahul Gondalia and Antoine Baldassari and Holliday, {Katelyn M.} and Justice, {Anne E.} and Ra{\'u}l M{\'e}ndez-Gir{\'a}ldez and Stewart, {James D.} and Duanping Liao and Yanosky, {Jeff D.} and Brennan, {Kasey J.M.} and Engel, {Stephanie M.} and Jordahl, {Kristina M.} and Elizabeth Kennedy and Ward-Caviness, {Cavin K.} and Kathrin Wolf and Melanie Waldenberger and Josef Cyrys and Annette Peters and Parveen Bhatti and Steve Horvath and Assimes, {Themistocles L.} and Pankow, {James S.} and Demerath, {Ellen W.} and Weihua Guan and Myriam Fornage and Jan Bressler and North, {Kari E.} and Conneely, {Karen N.} and Yun Li and Lifang Hou and Baccarelli, {Andrea A.} and Whitsel, {Eric A.}",
year = "2019",
month = "11",
doi = "10.1016/j.envint.2019.03.071",
language = "English (US)",
volume = "132",
journal = "Environmental International",
issn = "0160-4120",
publisher = "Elsevier Limited",

}

Gondalia, R, Baldassari, A, Holliday, KM, Justice, AE, Méndez-Giráldez, R, Stewart, JD, Liao, D, Yanosky, JD, Brennan, KJM, Engel, SM, Jordahl, KM, Kennedy, E, Ward-Caviness, CK, Wolf, K, Waldenberger, M, Cyrys, J, Peters, A, Bhatti, P, Horvath, S, Assimes, TL, Pankow, JS, Demerath, EW, Guan, W, Fornage, M, Bressler, J, North, KE, Conneely, KN, Li, Y, Hou, L, Baccarelli, AA & Whitsel, EA 2019, 'Methylome-wide association study provides evidence of particulate matter air pollution-associated DNA methylation', Environment International, vol. 132, 104723. https://doi.org/10.1016/j.envint.2019.03.071

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

In: Environment International, Vol. 132, 104723, 11.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Methylome-wide association study provides evidence of particulate matter air pollution-associated DNA methylation

AU - Gondalia, Rahul

AU - Baldassari, Antoine

AU - Holliday, Katelyn M.

AU - Justice, Anne E.

AU - Méndez-Giráldez, Raúl

AU - Stewart, James D.

AU - Liao, Duanping

AU - Yanosky, Jeff D.

AU - Brennan, Kasey J.M.

AU - Engel, Stephanie M.

AU - Jordahl, Kristina M.

AU - Kennedy, Elizabeth

AU - Ward-Caviness, Cavin K.

AU - Wolf, Kathrin

AU - Waldenberger, Melanie

AU - Cyrys, Josef

AU - Peters, Annette

AU - Bhatti, Parveen

AU - Horvath, Steve

AU - Assimes, Themistocles L.

AU - Pankow, James S.

AU - Demerath, Ellen W.

AU - Guan, Weihua

AU - Fornage, Myriam

AU - Bressler, Jan

AU - North, Kari E.

AU - Conneely, Karen N.

AU - Li, Yun

AU - Hou, Lifang

AU - Baccarelli, Andrea A.

AU - Whitsel, Eric A.

PY - 2019/11

Y1 - 2019/11

N2 - 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.

AB - 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.

KW - Air pollution

KW - DNA methylation

KW - Epigenetics

KW - Epigenome-wide association study

KW - Particulate matter

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U2 - 10.1016/j.envint.2019.03.071

DO - 10.1016/j.envint.2019.03.071

M3 - Article

C2 - 31208937

AN - SCOPUS:85067203949

VL - 132

JO - Environmental International

JF - Environmental International

SN - 0160-4120

M1 - 104723

ER -