Residential PM2.5 exposure and the nasal methylome in children

Joanne E Sordillo; Andres Cardenas; Cancan Qi; Sheryl L Rifas-Shiman; Brent Coull; Heike Luttmann-Gibson; Joel Schwartz; Itai Kloog; Marie-France Hivert; Dawn L DeMeo; Andrea A Baccarelli; Cheng-Jian Xu; Ulrike Gehring; Judith M Vonk; Gerard Koppelman; Emily Oken; Diane R Gold

doi:10.1016/j.envint.2021.106505

Residential PM2.5 exposure and the nasal methylome in children

Joanne E Sordillo, Andres Cardenas, Cancan Qi, Sheryl L Rifas-Shiman, Brent Coull, Heike Luttmann-Gibson, Joel Schwartz, Itai Kloog, Marie-France Hivert, Dawn L DeMeo, Andrea A Baccarelli, Cheng-Jian Xu, Ulrike Gehring, Judith M Vonk, Gerard Koppelman, Emily Oken, Diane R Gold

IRAS OH Epidemiology Chemical Agents

Harvard Pilgrim Health Care Institute
Wildlife Health Center, School of Veterinary Medicine, University of California, Davis, California.
University of Groningen, University Medical Center Groningen, Department of Paediatric Pulmonology and Paediatric Allergology, Beatrix Children's Hospital, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Harvard Medical School
Columbia University
Laboratory of Pediatric Infectious Diseases, Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands [email protected].

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

Abstract

Rationale: PM_2.5-induced adverse effects on respiratory health may be driven by epigenetic modifications in airway cells. The potential impact of exposure duration on epigenetic alterations in the airways is not yet known. Objectives: We aimed to study associations of fine particulate matter PM_2.5 exposure with DNA methylation in nasal cells. Methods: We conducted nasal epigenome-wide association analyses within 503 children from Project Viva (mean age 12.9 y), and examined various exposure durations (1-day, 1-week, 1-month, 3-months and 1-year) prior to nasal sampling. We used residential addresses to estimate average daily PM_2.5 at 1 km resolution. We collected nasal swabs from the anterior nares and measured DNA methylation (DNAm) using the Illumina MethylationEPIC BeadChip. We tested 719,075 high quality autosomal CpGs using CpG-by-CpG and regional DNAm analyses controlling for multiple comparisons, and adjusted for maternal education, household smokers, child sex, race/ethnicity, BMI z-score, age, season at sample collection and cell-type heterogeneity. We further corrected for bias and genomic inflation. We tested for replication in a cohort from the Netherlands (PIAMA). Results: In adjusted analyses, we found 362 CpGs associated with 1-year PM_2.5 (FDR < 0.05), 20 CpGs passing Bonferroni correction (P < 7.0x10^-8) and 10 Differentially Methylated Regions (DMRs). In 445 PIAMA participants (mean age 16.3 years) 11 of 203 available CpGs replicated at P < 0.05. We observed differential DNAm at/near genes implicated in cell cycle, immune and inflammatory responses. There were no CpGs or regions associated with PM_2.5 levels at 1-day, 1-week, or 1-month prior to sample collection, although 2 CpGs were associated with past 3-month PM_2.5. Conclusion: We observed wide-spread DNAm variability associated with average past year PM_2.5 exposure but we did not detect associations with shorter-term exposure. Our results suggest that nasal DNAm marks reflect chronic air pollution exposure.

Original language	English
Article number	106505
Pages (from-to)	1-9
Journal	Environment international
Volume	153
DOIs	https://doi.org/10.1016/j.envint.2021.106505
Publication status	Published - Aug 2021

Bibliographical note

Funding Information:
This research was supported by the National Institutes of Health grants R01 AI102960, R01 034568, UH3 OD023286, P30ES000002, R01HL111108, P01 HL132825, HL P01114501, R01 ES031259; and by the Environmental Protection Agency grants US EPA (R832416, RD834798). The PIAMA study was supported by The Netherlands Organization for Health Research and Development; The Netherlands Organization for Scientific Research; the Lung Foundation of the Netherlands (with methylation studies supported by AF 4.1.14.001); The Netherlands Ministry of Spatial Planning, Housing, and the Environment; and The Netherlands Ministry of Health, Welfare, and Sport. C.Q. was supported by a grant from the China Scholarship Council.

Publisher Copyright:
© 2021 The Authors

Keywords

Adolescent
Air Pollution/adverse effects
Child
DNA Methylation
Epigenome
Humans
Netherlands
Particulate Matter

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Cite this

Sordillo, J. E., Cardenas, A., Qi, C., Rifas-Shiman, S. L., Coull, B., Luttmann-Gibson, H., Schwartz, J., Kloog, I., Hivert, M.-F., DeMeo, D. L., Baccarelli, A. A., Xu, C.-J., Gehring, U., Vonk, J. M., Koppelman, G., Oken, E., & Gold, D. R. (2021). Residential PM2.5 exposure and the nasal methylome in children. Environment international, 153, 1-9. Article 106505. https://doi.org/10.1016/j.envint.2021.106505

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title = "Residential PM2.5 exposure and the nasal methylome in children",

abstract = "Rationale: PM2.5-induced adverse effects on respiratory health may be driven by epigenetic modifications in airway cells. The potential impact of exposure duration on epigenetic alterations in the airways is not yet known. Objectives: We aimed to study associations of fine particulate matter PM2.5 exposure with DNA methylation in nasal cells. Methods: We conducted nasal epigenome-wide association analyses within 503 children from Project Viva (mean age 12.9 y), and examined various exposure durations (1-day, 1-week, 1-month, 3-months and 1-year) prior to nasal sampling. We used residential addresses to estimate average daily PM2.5 at 1 km resolution. We collected nasal swabs from the anterior nares and measured DNA methylation (DNAm) using the Illumina MethylationEPIC BeadChip. We tested 719,075 high quality autosomal CpGs using CpG-by-CpG and regional DNAm analyses controlling for multiple comparisons, and adjusted for maternal education, household smokers, child sex, race/ethnicity, BMI z-score, age, season at sample collection and cell-type heterogeneity. We further corrected for bias and genomic inflation. We tested for replication in a cohort from the Netherlands (PIAMA). Results: In adjusted analyses, we found 362 CpGs associated with 1-year PM2.5 (FDR < 0.05), 20 CpGs passing Bonferroni correction (P < 7.0x10-8) and 10 Differentially Methylated Regions (DMRs). In 445 PIAMA participants (mean age 16.3 years) 11 of 203 available CpGs replicated at P < 0.05. We observed differential DNAm at/near genes implicated in cell cycle, immune and inflammatory responses. There were no CpGs or regions associated with PM2.5 levels at 1-day, 1-week, or 1-month prior to sample collection, although 2 CpGs were associated with past 3-month PM2.5. Conclusion: We observed wide-spread DNAm variability associated with average past year PM2.5 exposure but we did not detect associations with shorter-term exposure. Our results suggest that nasal DNAm marks reflect chronic air pollution exposure.",

keywords = "Adolescent, Air Pollution/adverse effects, Child, DNA Methylation, Epigenome, Humans, Netherlands, Particulate Matter",

author = "Sordillo, {Joanne E} and Andres Cardenas and Cancan Qi and Rifas-Shiman, {Sheryl L} and Brent Coull and Heike Luttmann-Gibson and Joel Schwartz and Itai Kloog and Marie-France Hivert and DeMeo, {Dawn L} and Baccarelli, {Andrea A} and Cheng-Jian Xu and Ulrike Gehring and Vonk, {Judith M} and Gerard Koppelman and Emily Oken and Gold, {Diane R}",

note = "Funding Information: This research was supported by the National Institutes of Health grants R01 AI102960, R01 034568, UH3 OD023286, P30ES000002, R01HL111108, P01 HL132825, HL P01114501, R01 ES031259; and by the Environmental Protection Agency grants US EPA (R832416, RD834798). The PIAMA study was supported by The Netherlands Organization for Health Research and Development; The Netherlands Organization for Scientific Research; the Lung Foundation of the Netherlands (with methylation studies supported by AF 4.1.14.001); The Netherlands Ministry of Spatial Planning, Housing, and the Environment; and The Netherlands Ministry of Health, Welfare, and Sport. C.Q. was supported by a grant from the China Scholarship Council. Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = aug,

doi = "10.1016/j.envint.2021.106505",

language = "English",

volume = "153",

pages = "1--9",

journal = "Environment international",

issn = "0160-4120",

publisher = "Elsevier Limited",

}

Sordillo, JE, Cardenas, A, Qi, C, Rifas-Shiman, SL, Coull, B, Luttmann-Gibson, H, Schwartz, J, Kloog, I, Hivert, M-F, DeMeo, DL, Baccarelli, AA, Xu, C-J, Gehring, U, Vonk, JM, Koppelman, G, Oken, E & Gold, DR 2021, 'Residential PM2.5 exposure and the nasal methylome in children', Environment international, vol. 153, 106505, pp. 1-9. https://doi.org/10.1016/j.envint.2021.106505

TY - JOUR

T1 - Residential PM2.5 exposure and the nasal methylome in children

AU - Sordillo, Joanne E

AU - Cardenas, Andres

AU - Qi, Cancan

AU - Rifas-Shiman, Sheryl L

AU - Coull, Brent

AU - Luttmann-Gibson, Heike

AU - Schwartz, Joel

AU - Kloog, Itai

AU - Hivert, Marie-France

AU - DeMeo, Dawn L

AU - Baccarelli, Andrea A

AU - Xu, Cheng-Jian

AU - Gehring, Ulrike

AU - Vonk, Judith M

AU - Koppelman, Gerard

AU - Oken, Emily

AU - Gold, Diane R

N1 - Funding Information: This research was supported by the National Institutes of Health grants R01 AI102960, R01 034568, UH3 OD023286, P30ES000002, R01HL111108, P01 HL132825, HL P01114501, R01 ES031259; and by the Environmental Protection Agency grants US EPA (R832416, RD834798). The PIAMA study was supported by The Netherlands Organization for Health Research and Development; The Netherlands Organization for Scientific Research; the Lung Foundation of the Netherlands (with methylation studies supported by AF 4.1.14.001); The Netherlands Ministry of Spatial Planning, Housing, and the Environment; and The Netherlands Ministry of Health, Welfare, and Sport. C.Q. was supported by a grant from the China Scholarship Council. Publisher Copyright: © 2021 The Authors

PY - 2021/8

Y1 - 2021/8

N2 - Rationale: PM2.5-induced adverse effects on respiratory health may be driven by epigenetic modifications in airway cells. The potential impact of exposure duration on epigenetic alterations in the airways is not yet known. Objectives: We aimed to study associations of fine particulate matter PM2.5 exposure with DNA methylation in nasal cells. Methods: We conducted nasal epigenome-wide association analyses within 503 children from Project Viva (mean age 12.9 y), and examined various exposure durations (1-day, 1-week, 1-month, 3-months and 1-year) prior to nasal sampling. We used residential addresses to estimate average daily PM2.5 at 1 km resolution. We collected nasal swabs from the anterior nares and measured DNA methylation (DNAm) using the Illumina MethylationEPIC BeadChip. We tested 719,075 high quality autosomal CpGs using CpG-by-CpG and regional DNAm analyses controlling for multiple comparisons, and adjusted for maternal education, household smokers, child sex, race/ethnicity, BMI z-score, age, season at sample collection and cell-type heterogeneity. We further corrected for bias and genomic inflation. We tested for replication in a cohort from the Netherlands (PIAMA). Results: In adjusted analyses, we found 362 CpGs associated with 1-year PM2.5 (FDR < 0.05), 20 CpGs passing Bonferroni correction (P < 7.0x10-8) and 10 Differentially Methylated Regions (DMRs). In 445 PIAMA participants (mean age 16.3 years) 11 of 203 available CpGs replicated at P < 0.05. We observed differential DNAm at/near genes implicated in cell cycle, immune and inflammatory responses. There were no CpGs or regions associated with PM2.5 levels at 1-day, 1-week, or 1-month prior to sample collection, although 2 CpGs were associated with past 3-month PM2.5. Conclusion: We observed wide-spread DNAm variability associated with average past year PM2.5 exposure but we did not detect associations with shorter-term exposure. Our results suggest that nasal DNAm marks reflect chronic air pollution exposure.

AB - Rationale: PM2.5-induced adverse effects on respiratory health may be driven by epigenetic modifications in airway cells. The potential impact of exposure duration on epigenetic alterations in the airways is not yet known. Objectives: We aimed to study associations of fine particulate matter PM2.5 exposure with DNA methylation in nasal cells. Methods: We conducted nasal epigenome-wide association analyses within 503 children from Project Viva (mean age 12.9 y), and examined various exposure durations (1-day, 1-week, 1-month, 3-months and 1-year) prior to nasal sampling. We used residential addresses to estimate average daily PM2.5 at 1 km resolution. We collected nasal swabs from the anterior nares and measured DNA methylation (DNAm) using the Illumina MethylationEPIC BeadChip. We tested 719,075 high quality autosomal CpGs using CpG-by-CpG and regional DNAm analyses controlling for multiple comparisons, and adjusted for maternal education, household smokers, child sex, race/ethnicity, BMI z-score, age, season at sample collection and cell-type heterogeneity. We further corrected for bias and genomic inflation. We tested for replication in a cohort from the Netherlands (PIAMA). Results: In adjusted analyses, we found 362 CpGs associated with 1-year PM2.5 (FDR < 0.05), 20 CpGs passing Bonferroni correction (P < 7.0x10-8) and 10 Differentially Methylated Regions (DMRs). In 445 PIAMA participants (mean age 16.3 years) 11 of 203 available CpGs replicated at P < 0.05. We observed differential DNAm at/near genes implicated in cell cycle, immune and inflammatory responses. There were no CpGs or regions associated with PM2.5 levels at 1-day, 1-week, or 1-month prior to sample collection, although 2 CpGs were associated with past 3-month PM2.5. Conclusion: We observed wide-spread DNAm variability associated with average past year PM2.5 exposure but we did not detect associations with shorter-term exposure. Our results suggest that nasal DNAm marks reflect chronic air pollution exposure.

KW - Adolescent

KW - Air Pollution/adverse effects

KW - Child

KW - DNA Methylation

KW - Epigenome

KW - Humans

KW - Netherlands

KW - Particulate Matter

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U2 - 10.1016/j.envint.2021.106505

DO - 10.1016/j.envint.2021.106505

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SN - 0160-4120

VL - 153

SP - 1

EP - 9

JO - Environment international

JF - Environment international

M1 - 106505

ER -

Residential PM2.5 exposure and the nasal methylome in children

Abstract

Bibliographical note

Keywords

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