Long-term outdoor air pollution and DNA methylation in circulating monocytes: Results from the Multi-Ethnic Study of Atherosclerosis (MESA)

Gloria C. Chi; Yongmei Liu; James W. MacDonald; R. Graham Barr; Kathleen M. Donohue; Mark D. Hensley; Lifang Hou; Charles E. McCall; Lindsay M. Reynolds; David S. Siscovick; Joel D. Kaufman

doi:10.1186/s12940-016-0202-4

Long-term outdoor air pollution and DNA methylation in circulating monocytes: Results from the Multi-Ethnic Study of Atherosclerosis (MESA)

Gloria C. Chi^*, Yongmei Liu, James W. MacDonald, R. Graham Barr, Kathleen M. Donohue, Mark D. Hensley, Lifang Hou, Charles E. McCall, Lindsay M. Reynolds, David S. Siscovick, Joel D. Kaufman

^*Corresponding author for this work

Preventive Medicine

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

45 Scopus citations

Abstract

Background: DNA methylation may mediate effects of air pollution on cardiovascular disease. The association between long-term air pollution exposure and DNA methylation in monocytes, which are central to atherosclerosis, has not been studied. We investigated the association between long-term ambient air pollution exposure and DNA methylation (candidate sites and global) in monocytes of adults (aged ≥55). Methods: One-year average ambient fine particulate matter (PM_2.5) and oxides of nitrogen (NO_X) concentrations were predicted at participants' (n = 1,207) addresses using spatiotemporal models. We assessed DNA methylation in circulating monocytes at 1) 2,713 CpG sites associated with mRNA expression of nearby genes and 2) probes mapping to Alu and LINE-1 repetitive elements (surrogates for global DNA methylation) using Illumina's Infinium HumanMethylation450 BeadChip. We used linear regression models adjusted for demographics, smoking, physical activity, socioeconomic status, methyl-nutrients, and technical variables. For significant air pollution-associated methylation sites, we also assessed the association between expression of gene transcripts previously associated with these CpG sites and air pollution. Results: At a false discovery rate of 0.05, five candidate CpGs (cg20455854, cg07855639, cg07598385, cg17360854, and cg23599683) had methylation significantly associated with PM_2.5 and none were associated with NO_X. Cg20455854 had the smallest p-value for the association with PM_2.5 (p = 2.77 × 10^-5). mRNA expression profiles of genes near three of the PM_2.5-associated CpGs (ANKHD1, LGALS2, and ANKRD11) were also significantly associated with PM_2.5 exposure. Alu and LINE-1 methylation were not associated with long-term air pollution exposure. Conclusions: We observed novel associations between long-term ambient air pollution exposure and site-specific DNA methylation, but not global DNA methylation, in purified monocytes of a multi-ethnic adult population. Epigenetic markers may provide insights into mechanisms underlying environmental factors in complex diseases like atherosclerosis.

Original language	English (US)
Article number	119
Journal	Environmental Health: A Global Access Science Source
Volume	15
Issue number	1
DOIs	https://doi.org/10.1186/s12940-016-0202-4
State	Published - Jan 12 2016

Keywords

ANKHD1
ANKRD11
Air pollution
BAZ2B
DNA methylation
LGALS2
NO
PM
PPIE

ASJC Scopus subject areas

Public Health, Environmental and Occupational Health
Health, Toxicology and Mutagenesis

UN SDGs

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

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10.1186/s12940-016-0202-4

Cite this

Chi, G. C., Liu, Y., MacDonald, J. W., Barr, R. G., Donohue, K. M., Hensley, M. D., Hou, L., McCall, C. E., Reynolds, L. M., Siscovick, D. S., & Kaufman, J. D. (2016). Long-term outdoor air pollution and DNA methylation in circulating monocytes: Results from the Multi-Ethnic Study of Atherosclerosis (MESA). Environmental Health: A Global Access Science Source, 15(1), [119]. https://doi.org/10.1186/s12940-016-0202-4

@article{7062318a140c4adeaad2655b04ee405e,

title = "Long-term outdoor air pollution and DNA methylation in circulating monocytes: Results from the Multi-Ethnic Study of Atherosclerosis (MESA)",

abstract = "Background: DNA methylation may mediate effects of air pollution on cardiovascular disease. The association between long-term air pollution exposure and DNA methylation in monocytes, which are central to atherosclerosis, has not been studied. We investigated the association between long-term ambient air pollution exposure and DNA methylation (candidate sites and global) in monocytes of adults (aged ≥55). Methods: One-year average ambient fine particulate matter (PM2.5) and oxides of nitrogen (NOX) concentrations were predicted at participants' (n = 1,207) addresses using spatiotemporal models. We assessed DNA methylation in circulating monocytes at 1) 2,713 CpG sites associated with mRNA expression of nearby genes and 2) probes mapping to Alu and LINE-1 repetitive elements (surrogates for global DNA methylation) using Illumina's Infinium HumanMethylation450 BeadChip. We used linear regression models adjusted for demographics, smoking, physical activity, socioeconomic status, methyl-nutrients, and technical variables. For significant air pollution-associated methylation sites, we also assessed the association between expression of gene transcripts previously associated with these CpG sites and air pollution. Results: At a false discovery rate of 0.05, five candidate CpGs (cg20455854, cg07855639, cg07598385, cg17360854, and cg23599683) had methylation significantly associated with PM2.5 and none were associated with NOX. Cg20455854 had the smallest p-value for the association with PM2.5 (p = 2.77 × 10-5). mRNA expression profiles of genes near three of the PM2.5-associated CpGs (ANKHD1, LGALS2, and ANKRD11) were also significantly associated with PM2.5 exposure. Alu and LINE-1 methylation were not associated with long-term air pollution exposure. Conclusions: We observed novel associations between long-term ambient air pollution exposure and site-specific DNA methylation, but not global DNA methylation, in purified monocytes of a multi-ethnic adult population. Epigenetic markers may provide insights into mechanisms underlying environmental factors in complex diseases like atherosclerosis.",

keywords = "ANKHD1, ANKRD11, Air pollution, BAZ2B, DNA methylation, LGALS2, NO, PM, PPIE",

author = "Chi, {Gloria C.} and Yongmei Liu and MacDonald, {James W.} and Barr, {R. Graham} and Donohue, {Kathleen M.} and Hensley, {Mark D.} and Lifang Hou and McCall, {Charles E.} and Reynolds, {Lindsay M.} and Siscovick, {David S.} and Kaufman, {Joel D.}",

note = "Funding Information: This work was supported by National Institute of Environmental Health Sciences (NIEHS, 1 F31 ES025475-01, P30 ES007033, P50 ES015915-01). This research was also supported by contracts T32 HL007902, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, and 2R01 HL071759 from the National Heart, Lung, and Blood Institute and by grants UL1-TR-000040 and UL1-TR-001079 from NCRR. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. This publication was developed under a STAR research assistance agreement, No. RD831697 (MESA Air), awarded by the U.S Environmental protection Agency. It has not been formally reviewed by the EPA. The views expressed in this document are solely those of the authors and the EPA does not endorse any products or commercial services mentioned in this publication. The MESA Epigenomics & Transcriptomics Study was funded by NHLBI grant 1R01HL101250-01 to Wake Forest University Health Sciences. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NHLBI, USEPA, or NIEHS. Publisher Copyright: {\textcopyright} 2016 The Author(s).",

year = "2016",

month = jan,

day = "12",

doi = "10.1186/s12940-016-0202-4",

language = "English (US)",

volume = "15",

journal = "Environmental Health: A Global Access Science Source",

issn = "1476-069X",

publisher = "BioMed Central",

number = "1",

}

Chi, GC, Liu, Y, MacDonald, JW, Barr, RG, Donohue, KM, Hensley, MD, Hou, L, McCall, CE, Reynolds, LM, Siscovick, DS & Kaufman, JD 2016, 'Long-term outdoor air pollution and DNA methylation in circulating monocytes: Results from the Multi-Ethnic Study of Atherosclerosis (MESA)', Environmental Health: A Global Access Science Source, vol. 15, no. 1, 119. https://doi.org/10.1186/s12940-016-0202-4

TY - JOUR

T1 - Long-term outdoor air pollution and DNA methylation in circulating monocytes

T2 - Results from the Multi-Ethnic Study of Atherosclerosis (MESA)

AU - Chi, Gloria C.

AU - Liu, Yongmei

AU - MacDonald, James W.

AU - Barr, R. Graham

AU - Donohue, Kathleen M.

AU - Hensley, Mark D.

AU - Hou, Lifang

AU - McCall, Charles E.

AU - Reynolds, Lindsay M.

AU - Siscovick, David S.

AU - Kaufman, Joel D.

N1 - Funding Information: This work was supported by National Institute of Environmental Health Sciences (NIEHS, 1 F31 ES025475-01, P30 ES007033, P50 ES015915-01). This research was also supported by contracts T32 HL007902, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, and 2R01 HL071759 from the National Heart, Lung, and Blood Institute and by grants UL1-TR-000040 and UL1-TR-001079 from NCRR. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. This publication was developed under a STAR research assistance agreement, No. RD831697 (MESA Air), awarded by the U.S Environmental protection Agency. It has not been formally reviewed by the EPA. The views expressed in this document are solely those of the authors and the EPA does not endorse any products or commercial services mentioned in this publication. The MESA Epigenomics & Transcriptomics Study was funded by NHLBI grant 1R01HL101250-01 to Wake Forest University Health Sciences. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NHLBI, USEPA, or NIEHS. Publisher Copyright: © 2016 The Author(s).

PY - 2016/1/12

Y1 - 2016/1/12

N2 - Background: DNA methylation may mediate effects of air pollution on cardiovascular disease. The association between long-term air pollution exposure and DNA methylation in monocytes, which are central to atherosclerosis, has not been studied. We investigated the association between long-term ambient air pollution exposure and DNA methylation (candidate sites and global) in monocytes of adults (aged ≥55). Methods: One-year average ambient fine particulate matter (PM2.5) and oxides of nitrogen (NOX) concentrations were predicted at participants' (n = 1,207) addresses using spatiotemporal models. We assessed DNA methylation in circulating monocytes at 1) 2,713 CpG sites associated with mRNA expression of nearby genes and 2) probes mapping to Alu and LINE-1 repetitive elements (surrogates for global DNA methylation) using Illumina's Infinium HumanMethylation450 BeadChip. We used linear regression models adjusted for demographics, smoking, physical activity, socioeconomic status, methyl-nutrients, and technical variables. For significant air pollution-associated methylation sites, we also assessed the association between expression of gene transcripts previously associated with these CpG sites and air pollution. Results: At a false discovery rate of 0.05, five candidate CpGs (cg20455854, cg07855639, cg07598385, cg17360854, and cg23599683) had methylation significantly associated with PM2.5 and none were associated with NOX. Cg20455854 had the smallest p-value for the association with PM2.5 (p = 2.77 × 10-5). mRNA expression profiles of genes near three of the PM2.5-associated CpGs (ANKHD1, LGALS2, and ANKRD11) were also significantly associated with PM2.5 exposure. Alu and LINE-1 methylation were not associated with long-term air pollution exposure. Conclusions: We observed novel associations between long-term ambient air pollution exposure and site-specific DNA methylation, but not global DNA methylation, in purified monocytes of a multi-ethnic adult population. Epigenetic markers may provide insights into mechanisms underlying environmental factors in complex diseases like atherosclerosis.

AB - Background: DNA methylation may mediate effects of air pollution on cardiovascular disease. The association between long-term air pollution exposure and DNA methylation in monocytes, which are central to atherosclerosis, has not been studied. We investigated the association between long-term ambient air pollution exposure and DNA methylation (candidate sites and global) in monocytes of adults (aged ≥55). Methods: One-year average ambient fine particulate matter (PM2.5) and oxides of nitrogen (NOX) concentrations were predicted at participants' (n = 1,207) addresses using spatiotemporal models. We assessed DNA methylation in circulating monocytes at 1) 2,713 CpG sites associated with mRNA expression of nearby genes and 2) probes mapping to Alu and LINE-1 repetitive elements (surrogates for global DNA methylation) using Illumina's Infinium HumanMethylation450 BeadChip. We used linear regression models adjusted for demographics, smoking, physical activity, socioeconomic status, methyl-nutrients, and technical variables. For significant air pollution-associated methylation sites, we also assessed the association between expression of gene transcripts previously associated with these CpG sites and air pollution. Results: At a false discovery rate of 0.05, five candidate CpGs (cg20455854, cg07855639, cg07598385, cg17360854, and cg23599683) had methylation significantly associated with PM2.5 and none were associated with NOX. Cg20455854 had the smallest p-value for the association with PM2.5 (p = 2.77 × 10-5). mRNA expression profiles of genes near three of the PM2.5-associated CpGs (ANKHD1, LGALS2, and ANKRD11) were also significantly associated with PM2.5 exposure. Alu and LINE-1 methylation were not associated with long-term air pollution exposure. Conclusions: We observed novel associations between long-term ambient air pollution exposure and site-specific DNA methylation, but not global DNA methylation, in purified monocytes of a multi-ethnic adult population. Epigenetic markers may provide insights into mechanisms underlying environmental factors in complex diseases like atherosclerosis.

KW - ANKHD1

KW - ANKRD11

KW - Air pollution

KW - BAZ2B

KW - DNA methylation

KW - LGALS2

KW - NO

KW - PM

KW - PPIE

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U2 - 10.1186/s12940-016-0202-4

DO - 10.1186/s12940-016-0202-4

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SN - 1476-069X

VL - 15

JO - Environmental Health: A Global Access Science Source

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ER -

Long-term outdoor air pollution and DNA methylation in circulating monocytes: Results from the Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract

Keywords

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UN SDGs

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