Acute changes in DNA methylation in relation to 24 h personal air pollution exposure measurements: A panel study in four European countries

Nahid Mostafavi; Roel Vermeulen; Akram Ghantous; Gerard Hoek; Nicole Probst-Hensch; Zdenko Herceg; Sonia Tarallo; Alessio Naccarati; Jos C. S. Kleinjans; Medea Imboden; Ayoung Jeong; David Morley; Andre F. S. Amaral; Erik van Nunen; John Gulliver; Marc Chadeau-Hyam; Paolo Vineis; Jelle Vlaanderen

doi:10.1016/j.envint.2018.07.026

Acute changes in DNA methylation in relation to 24 h personal air pollution exposure measurements: A panel study in four European countries

Nahid Mostafavi, Roel Vermeulen, Akram Ghantous, Gerard Hoek, Nicole Probst-Hensch, Zdenko Herceg, Sonia Tarallo, Alessio Naccarati, Jos C. S. Kleinjans, Medea Imboden, Ayoung Jeong, David Morley, Andre F. S. Amaral, Erik van Nunen, John Gulliver, Marc Chadeau-Hyam, Paolo Vineis, Jelle Vlaanderen^*

^*Corresponding author for this work

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

Abstract

Background: One of the potential mechanisms linking air pollution to health effects is through changes in DNA-methylation, which so far has mainly been analyzed globally or at candidate sites.

Objective: We investigated the association of personal and ambient air pollution exposure measures with genome-wide DNA-methylation changes.

Methods: We collected repeated 24-hour personal and ambient exposure measurements of particulate matter (PM2.5), PM2.5 absorbance, and ultrafine particles (UFP) and peripheral blood samples from a panel of 157 healthy non-smoking adults living in four European countries. We applied univariate mixed-effects models to investigate the association between air pollution and genome-wide DNA-methylation perturbations at single CpG (cytosine-guanine dinucleotide) sites and in Differentially Methylated Regions (DMRs). Subsequently, we explored the association of air pollution-induced methylation alterations with gene expression and serum immune marker levels measured in the same subjects.

Results: Personal exposure to PM2.5 was associated with methylation changes at 13 CpG sites and 69 DMRs. Two of the 13 identified CpG sites (mapped to genes KNDC1 and FAM50B) were located within these DMRs. In addition, 42 DMRs were associated with personal PM2.5 absorbance exposure, 16 DMRs with personal exposure to UFP, 4 DMRs with ambient exposure to PM2.5, 16 DMRs with ambient PM2.5 absorbance exposure, and 15 DMRs with ambient UFP exposure. Correlation between methylation levels at identified CpG sites and gene expression and immune markers was generally moderate.

Conclusion: This study provides evidence for an association between 24-hour exposure to air pollution and DNA-methylation at single sites and regional clusters of CpGs. Analysis of differentially methylated regions provides a promising avenue to further explore the subtle impact of environmental exposures on DNA-methylation.

Original language	English
Pages (from-to)	11-21
Number of pages	11
Journal	Environment International
Volume	120
DOIs	https://doi.org/10.1016/j.envint.2018.07.026
Publication status	Published - Nov 2018

Keywords

DNA-methylation
Air pollution
Fine particles
Ultrafine particles
Immune markers
GENOME-BROWSER DATABASE
FINE PARTICULATE MATTER
GENE-EXPRESSION
DIESEL EXHAUST
SOFTWARE
MODELS
HEALTH
ABSORBENCY
BIOMARKERS
MEDIATION

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Mostafavi, N., Vermeulen, R., Ghantous, A., Hoek, G., Probst-Hensch, N., Herceg, Z., Tarallo, S., Naccarati, A., Kleinjans, J. C. S., Imboden, M., Jeong, A., Morley, D., Amaral, A. F. S., van Nunen, E., Gulliver, J., Chadeau-Hyam, M., Vineis, P., & Vlaanderen, J. (2018). Acute changes in DNA methylation in relation to 24 h personal air pollution exposure measurements: A panel study in four European countries. Environment International, 120, 11-21. https://doi.org/10.1016/j.envint.2018.07.026

@article{42a612a643094ad1892b0040bef743f6,

title = "Acute changes in DNA methylation in relation to 24 h personal air pollution exposure measurements: A panel study in four European countries",

abstract = "Background: One of the potential mechanisms linking air pollution to health effects is through changes in DNA-methylation, which so far has mainly been analyzed globally or at candidate sites.Objective: We investigated the association of personal and ambient air pollution exposure measures with genome-wide DNA-methylation changes.Methods: We collected repeated 24-hour personal and ambient exposure measurements of particulate matter (PM2.5), PM2.5 absorbance, and ultrafine particles (UFP) and peripheral blood samples from a panel of 157 healthy non-smoking adults living in four European countries. We applied univariate mixed-effects models to investigate the association between air pollution and genome-wide DNA-methylation perturbations at single CpG (cytosine-guanine dinucleotide) sites and in Differentially Methylated Regions (DMRs). Subsequently, we explored the association of air pollution-induced methylation alterations with gene expression and serum immune marker levels measured in the same subjects.Results: Personal exposure to PM2.5 was associated with methylation changes at 13 CpG sites and 69 DMRs. Two of the 13 identified CpG sites (mapped to genes KNDC1 and FAM50B) were located within these DMRs. In addition, 42 DMRs were associated with personal PM2.5 absorbance exposure, 16 DMRs with personal exposure to UFP, 4 DMRs with ambient exposure to PM2.5, 16 DMRs with ambient PM2.5 absorbance exposure, and 15 DMRs with ambient UFP exposure. Correlation between methylation levels at identified CpG sites and gene expression and immune markers was generally moderate.Conclusion: This study provides evidence for an association between 24-hour exposure to air pollution and DNA-methylation at single sites and regional clusters of CpGs. Analysis of differentially methylated regions provides a promising avenue to further explore the subtle impact of environmental exposures on DNA-methylation.",

keywords = "DNA-methylation, Air pollution, Fine particles, Ultrafine particles, Immune markers, GENOME-BROWSER DATABASE, FINE PARTICULATE MATTER, GENE-EXPRESSION, DIESEL EXHAUST, SOFTWARE, MODELS, HEALTH, ABSORBENCY, BIOMARKERS, MEDIATION",

author = "Nahid Mostafavi and Roel Vermeulen and Akram Ghantous and Gerard Hoek and Nicole Probst-Hensch and Zdenko Herceg and Sonia Tarallo and Alessio Naccarati and Kleinjans, {Jos C. S.} and Medea Imboden and Ayoung Jeong and David Morley and Amaral, {Andre F. S.} and {van Nunen}, Erik and John Gulliver and Marc Chadeau-Hyam and Paolo Vineis and Jelle Vlaanderen",

year = "2018",

month = nov,

doi = "10.1016/j.envint.2018.07.026",

language = "English",

volume = "120",

pages = "11--21",

journal = "Environment International",

issn = "0160-4120",

publisher = "Elsevier Science",

}

Mostafavi, N, Vermeulen, R, Ghantous, A, Hoek, G, Probst-Hensch, N, Herceg, Z, Tarallo, S, Naccarati, A, Kleinjans, JCS, Imboden, M, Jeong, A, Morley, D, Amaral, AFS, van Nunen, E, Gulliver, J, Chadeau-Hyam, M, Vineis, P & Vlaanderen, J 2018, 'Acute changes in DNA methylation in relation to 24 h personal air pollution exposure measurements: A panel study in four European countries', Environment International, vol. 120, pp. 11-21. https://doi.org/10.1016/j.envint.2018.07.026

TY - JOUR

T1 - Acute changes in DNA methylation in relation to 24 h personal air pollution exposure measurements

T2 - A panel study in four European countries

AU - Mostafavi, Nahid

AU - Vermeulen, Roel

AU - Ghantous, Akram

AU - Hoek, Gerard

AU - Probst-Hensch, Nicole

AU - Herceg, Zdenko

AU - Tarallo, Sonia

AU - Naccarati, Alessio

AU - Kleinjans, Jos C. S.

AU - Imboden, Medea

AU - Jeong, Ayoung

AU - Morley, David

AU - Amaral, Andre F. S.

AU - van Nunen, Erik

AU - Gulliver, John

AU - Chadeau-Hyam, Marc

AU - Vineis, Paolo

AU - Vlaanderen, Jelle

PY - 2018/11

Y1 - 2018/11

N2 - Background: One of the potential mechanisms linking air pollution to health effects is through changes in DNA-methylation, which so far has mainly been analyzed globally or at candidate sites.Objective: We investigated the association of personal and ambient air pollution exposure measures with genome-wide DNA-methylation changes.Methods: We collected repeated 24-hour personal and ambient exposure measurements of particulate matter (PM2.5), PM2.5 absorbance, and ultrafine particles (UFP) and peripheral blood samples from a panel of 157 healthy non-smoking adults living in four European countries. We applied univariate mixed-effects models to investigate the association between air pollution and genome-wide DNA-methylation perturbations at single CpG (cytosine-guanine dinucleotide) sites and in Differentially Methylated Regions (DMRs). Subsequently, we explored the association of air pollution-induced methylation alterations with gene expression and serum immune marker levels measured in the same subjects.Results: Personal exposure to PM2.5 was associated with methylation changes at 13 CpG sites and 69 DMRs. Two of the 13 identified CpG sites (mapped to genes KNDC1 and FAM50B) were located within these DMRs. In addition, 42 DMRs were associated with personal PM2.5 absorbance exposure, 16 DMRs with personal exposure to UFP, 4 DMRs with ambient exposure to PM2.5, 16 DMRs with ambient PM2.5 absorbance exposure, and 15 DMRs with ambient UFP exposure. Correlation between methylation levels at identified CpG sites and gene expression and immune markers was generally moderate.Conclusion: This study provides evidence for an association between 24-hour exposure to air pollution and DNA-methylation at single sites and regional clusters of CpGs. Analysis of differentially methylated regions provides a promising avenue to further explore the subtle impact of environmental exposures on DNA-methylation.

AB - Background: One of the potential mechanisms linking air pollution to health effects is through changes in DNA-methylation, which so far has mainly been analyzed globally or at candidate sites.Objective: We investigated the association of personal and ambient air pollution exposure measures with genome-wide DNA-methylation changes.Methods: We collected repeated 24-hour personal and ambient exposure measurements of particulate matter (PM2.5), PM2.5 absorbance, and ultrafine particles (UFP) and peripheral blood samples from a panel of 157 healthy non-smoking adults living in four European countries. We applied univariate mixed-effects models to investigate the association between air pollution and genome-wide DNA-methylation perturbations at single CpG (cytosine-guanine dinucleotide) sites and in Differentially Methylated Regions (DMRs). Subsequently, we explored the association of air pollution-induced methylation alterations with gene expression and serum immune marker levels measured in the same subjects.Results: Personal exposure to PM2.5 was associated with methylation changes at 13 CpG sites and 69 DMRs. Two of the 13 identified CpG sites (mapped to genes KNDC1 and FAM50B) were located within these DMRs. In addition, 42 DMRs were associated with personal PM2.5 absorbance exposure, 16 DMRs with personal exposure to UFP, 4 DMRs with ambient exposure to PM2.5, 16 DMRs with ambient PM2.5 absorbance exposure, and 15 DMRs with ambient UFP exposure. Correlation between methylation levels at identified CpG sites and gene expression and immune markers was generally moderate.Conclusion: This study provides evidence for an association between 24-hour exposure to air pollution and DNA-methylation at single sites and regional clusters of CpGs. Analysis of differentially methylated regions provides a promising avenue to further explore the subtle impact of environmental exposures on DNA-methylation.

KW - DNA-methylation

KW - Air pollution

KW - Fine particles

KW - Ultrafine particles

KW - Immune markers

KW - GENOME-BROWSER DATABASE

KW - FINE PARTICULATE MATTER

KW - GENE-EXPRESSION

KW - DIESEL EXHAUST

KW - SOFTWARE

KW - MODELS

KW - HEALTH

KW - ABSORBENCY

KW - BIOMARKERS

KW - MEDIATION

U2 - 10.1016/j.envint.2018.07.026

DO - 10.1016/j.envint.2018.07.026

M3 - Article

C2 - 30055357

SN - 0160-4120

VL - 120

SP - 11

EP - 21

JO - Environment International

JF - Environment International

ER -