Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure

Olena Gruzieva; Cheng-Jian Xu; Carrie V. Breton; Isabella Annesi-Maesano; Josep M. Anto; Charles Auffray; Stephane Ballereau; Tom Bellander; Jean Bousquet; Mariona Bustamante; Marie-Aline Charles; Yvonne de Kluizenaar; Herman T. den Dekker; Liesbeth Duijts; Janine F. Felix; Ulrike Gehring; Monica Guxens; Vincent V. W. Jaddoe; Soesma A. Jankipersadsing; Simon Kebede Merid; Juha Kere; Ashish Kumar; Nathanael Lemonnier; Johanna Lepeule; Wenche Nystad; Christian Magnus Page; Sviatlana Panasevich; Dirkje Postma; Remy Slama; Jordi Sunyer; Cilla Soderhall; Jin Yao; Stephanie J. London; Goran Pershagen; Gerard H. Koppelman; Erik Melen

doi:10.1289/EHP36

Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure

Olena Gruzieva^*, Cheng-Jian Xu, Carrie V. Breton, Isabella Annesi-Maesano, Josep M. Anto, Charles Auffray, Stephane Ballereau, Tom Bellander, Jean Bousquet, Mariona Bustamante, Marie-Aline Charles, Yvonne de Kluizenaar, Herman T. den Dekker, Liesbeth Duijts, Janine F. Felix, Ulrike Gehring, Monica Guxens, Vincent V. W. Jaddoe, Soesma A. Jankipersadsing, Simon Kebede MeridJuha Kere, Ashish Kumar, Nathanael Lemonnier, Johanna Lepeule, Wenche Nystad, Christian Magnus Page, Sviatlana Panasevich, Dirkje Postma, Remy Slama, Jordi Sunyer, Cilla Soderhall, Jin Yao, Stephanie J. London, Goran Pershagen, Gerard H. Koppelman, Erik Melen

^*Corresponding author for this work

Groningen Research Institute for Asthma and COPD (GRIAC)

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

98 Citations (Scopus)

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Abstract

BACKGROUND: Prenatal exposure to air pollution is considered to be associated with adverse effects on child health. This may partly be mediated by mechanisms related to DNA methylation.

OBJECTIVES: We investigated associations between exposure to air pollution, using nitrogen dioxide (NO2) as marker, and epigenome-wide cord blood DNA methylation.

METHODS: We meta-analyzed the associations between NO2 exposure at residential addresses during pregnancy and cord blood DNA methylation (Illumina 450K) in four European and North American studies (n = 1,508) with subsequent look-up analyses in children ages 4 (n = 733) and 8 (n = 786) years. Additionally, we applied a literature-based candidate approach for antioxidant and anti-inflammatory genes. To assess influence of exposure at the transcriptomics level, we related mRNA expression in blood cells to NO2 exposure in 4- (n = 111) and 16-year-olds (n = 239).

RESULTS: We found epigenome-wide significant associations [false discovery rate (FDR) p <0.05] between maternal NO2 exposure during pregnancy and DNA methylation in newborns for 3 CpG sites in mitochondria-related genes: cg12283362 (LONP1), cg24172570 (3.8 kbp upstream of HIBADH), and cg08973675 (SLC25A28). The associations with cg08973675 methylation were also significant in the older children. Further analysis of antioxidant and anti-inflammatory genes revealed differentially methylated CpGs in CAT and TPO in newborns (FDR p <0.05). NO2 exposure at the time of biosampling in childhood had a significant impact on CAT and TPO expression.

CONCLUSIONS: NO2 exposure during pregnancy was associated with differential offspring DNA methylation in mitochondria-related genes. Exposure to NO2 was also linked to differential methylation as well as expression of genes involved in antioxidant defense pathways.

Original language	English
Pages (from-to)	104-110
Number of pages	7
Journal	Environmental Health Perspectives
Volume	125
Issue number	1
DOIs	https://doi.org/10.1289/EHP36
Publication status	Published - Jan-2017

Keywords

POLYCYCLIC AROMATIC-HYDROCARBONS
DNA METHYLATION
QUANTILE NORMALIZATION
RESPIRATORY HEALTH
OXIDATIVE STRESS
MATERNAL SMOKING
CORD BLOOD
EARLY-LIFE
ASTHMA
ASSOCIATION

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Gruzieva, O., Xu, C-J., Breton, C. V., Annesi-Maesano, I., Anto, J. M., Auffray, C., Ballereau, S., Bellander, T., Bousquet, J., Bustamante, M., Charles, M-A., de Kluizenaar, Y., den Dekker, H. T., Duijts, L., Felix, J. F., Gehring, U., Guxens, M., Jaddoe, V. V. W., Jankipersadsing, S. A., ... Melen, E. (2017). Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure. Environmental Health Perspectives, 125(1), 104-110. https://doi.org/10.1289/EHP36

Gruzieva, Olena ; Xu, Cheng-Jian ; Breton, Carrie V. ; Annesi-Maesano, Isabella ; Anto, Josep M. ; Auffray, Charles ; Ballereau, Stephane ; Bellander, Tom ; Bousquet, Jean ; Bustamante, Mariona ; Charles, Marie-Aline ; de Kluizenaar, Yvonne ; den Dekker, Herman T. ; Duijts, Liesbeth ; Felix, Janine F. ; Gehring, Ulrike ; Guxens, Monica ; Jaddoe, Vincent V. W. ; Jankipersadsing, Soesma A. ; Merid, Simon Kebede ; Kere, Juha ; Kumar, Ashish ; Lemonnier, Nathanael ; Lepeule, Johanna ; Nystad, Wenche ; Page, Christian Magnus ; Panasevich, Sviatlana ; Postma, Dirkje ; Slama, Remy ; Sunyer, Jordi ; Soderhall, Cilla ; Yao, Jin ; London, Stephanie J. ; Pershagen, Goran ; Koppelman, Gerard H. ; Melen, Erik. / Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure. In: Environmental Health Perspectives. 2017 ; Vol. 125, No. 1. pp. 104-110.

@article{fce930b767c240b9a8b3f1c6e3520e94,

title = "Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure",

abstract = "BACKGROUND: Prenatal exposure to air pollution is considered to be associated with adverse effects on child health. This may partly be mediated by mechanisms related to DNA methylation.OBJECTIVES: We investigated associations between exposure to air pollution, using nitrogen dioxide (NO2) as marker, and epigenome-wide cord blood DNA methylation.METHODS: We meta-analyzed the associations between NO2 exposure at residential addresses during pregnancy and cord blood DNA methylation (Illumina 450K) in four European and North American studies (n = 1,508) with subsequent look-up analyses in children ages 4 (n = 733) and 8 (n = 786) years. Additionally, we applied a literature-based candidate approach for antioxidant and anti-inflammatory genes. To assess influence of exposure at the transcriptomics level, we related mRNA expression in blood cells to NO2 exposure in 4- (n = 111) and 16-year-olds (n = 239).RESULTS: We found epigenome-wide significant associations [false discovery rate (FDR) p <0.05] between maternal NO2 exposure during pregnancy and DNA methylation in newborns for 3 CpG sites in mitochondria-related genes: cg12283362 (LONP1), cg24172570 (3.8 kbp upstream of HIBADH), and cg08973675 (SLC25A28). The associations with cg08973675 methylation were also significant in the older children. Further analysis of antioxidant and anti-inflammatory genes revealed differentially methylated CpGs in CAT and TPO in newborns (FDR p <0.05). NO2 exposure at the time of biosampling in childhood had a significant impact on CAT and TPO expression.CONCLUSIONS: NO2 exposure during pregnancy was associated with differential offspring DNA methylation in mitochondria-related genes. Exposure to NO2 was also linked to differential methylation as well as expression of genes involved in antioxidant defense pathways.",

keywords = "POLYCYCLIC AROMATIC-HYDROCARBONS, DNA METHYLATION, QUANTILE NORMALIZATION, RESPIRATORY HEALTH, OXIDATIVE STRESS, MATERNAL SMOKING, CORD BLOOD, EARLY-LIFE, ASTHMA, ASSOCIATION",

author = "Olena Gruzieva and Cheng-Jian Xu and Breton, {Carrie V.} and Isabella Annesi-Maesano and Anto, {Josep M.} and Charles Auffray and Stephane Ballereau and Tom Bellander and Jean Bousquet and Mariona Bustamante and Marie-Aline Charles and {de Kluizenaar}, Yvonne and {den Dekker}, {Herman T.} and Liesbeth Duijts and Felix, {Janine F.} and Ulrike Gehring and Monica Guxens and Jaddoe, {Vincent V. W.} and Jankipersadsing, {Soesma A.} and Merid, {Simon Kebede} and Juha Kere and Ashish Kumar and Nathanael Lemonnier and Johanna Lepeule and Wenche Nystad and Page, {Christian Magnus} and Sviatlana Panasevich and Dirkje Postma and Remy Slama and Jordi Sunyer and Cilla Soderhall and Jin Yao and London, {Stephanie J.} and Goran Pershagen and Koppelman, {Gerard H.} and Erik Melen",

year = "2017",

month = jan,

doi = "10.1289/EHP36",

language = "English",

volume = "125",

pages = "104--110",

journal = "Environmental Health Perspectives",

issn = "0091-6765",

publisher = "US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE",

number = "1",

}

Gruzieva, O, Xu, C-J, Breton, CV, Annesi-Maesano, I, Anto, JM, Auffray, C, Ballereau, S, Bellander, T, Bousquet, J, Bustamante, M, Charles, M-A, de Kluizenaar, Y, den Dekker, HT, Duijts, L, Felix, JF, Gehring, U, Guxens, M, Jaddoe, VVW, Jankipersadsing, SA, Merid, SK, Kere, J, Kumar, A, Lemonnier, N, Lepeule, J, Nystad, W, Page, CM, Panasevich, S, Postma, D, Slama, R, Sunyer, J, Soderhall, C, Yao, J, London, SJ, Pershagen, G, Koppelman, GH & Melen, E 2017, 'Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure', Environmental Health Perspectives, vol. 125, no. 1, pp. 104-110. https://doi.org/10.1289/EHP36

Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure. / Gruzieva, Olena; Xu, Cheng-Jian; Breton, Carrie V.; Annesi-Maesano, Isabella; Anto, Josep M.; Auffray, Charles; Ballereau, Stephane; Bellander, Tom; Bousquet, Jean; Bustamante, Mariona; Charles, Marie-Aline; de Kluizenaar, Yvonne; den Dekker, Herman T.; Duijts, Liesbeth; Felix, Janine F.; Gehring, Ulrike; Guxens, Monica; Jaddoe, Vincent V. W.; Jankipersadsing, Soesma A.; Merid, Simon Kebede; Kere, Juha; Kumar, Ashish; Lemonnier, Nathanael; Lepeule, Johanna; Nystad, Wenche; Page, Christian Magnus; Panasevich, Sviatlana; Postma, Dirkje; Slama, Remy; Sunyer, Jordi; Soderhall, Cilla; Yao, Jin; London, Stephanie J.; Pershagen, Goran; Koppelman, Gerard H.; Melen, Erik.

In: Environmental Health Perspectives, Vol. 125, No. 1, 01.2017, p. 104-110.

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

TY - JOUR

T1 - Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure

AU - Gruzieva, Olena

AU - Xu, Cheng-Jian

AU - Breton, Carrie V.

AU - Annesi-Maesano, Isabella

AU - Anto, Josep M.

AU - Auffray, Charles

AU - Ballereau, Stephane

AU - Bellander, Tom

AU - Bousquet, Jean

AU - Bustamante, Mariona

AU - Charles, Marie-Aline

AU - de Kluizenaar, Yvonne

AU - den Dekker, Herman T.

AU - Duijts, Liesbeth

AU - Felix, Janine F.

AU - Gehring, Ulrike

AU - Guxens, Monica

AU - Jaddoe, Vincent V. W.

AU - Jankipersadsing, Soesma A.

AU - Merid, Simon Kebede

AU - Kere, Juha

AU - Kumar, Ashish

AU - Lemonnier, Nathanael

AU - Lepeule, Johanna

AU - Nystad, Wenche

AU - Page, Christian Magnus

AU - Panasevich, Sviatlana

AU - Postma, Dirkje

AU - Slama, Remy

AU - Sunyer, Jordi

AU - Soderhall, Cilla

AU - Yao, Jin

AU - London, Stephanie J.

AU - Pershagen, Goran

AU - Koppelman, Gerard H.

AU - Melen, Erik

PY - 2017/1

Y1 - 2017/1

N2 - BACKGROUND: Prenatal exposure to air pollution is considered to be associated with adverse effects on child health. This may partly be mediated by mechanisms related to DNA methylation.OBJECTIVES: We investigated associations between exposure to air pollution, using nitrogen dioxide (NO2) as marker, and epigenome-wide cord blood DNA methylation.METHODS: We meta-analyzed the associations between NO2 exposure at residential addresses during pregnancy and cord blood DNA methylation (Illumina 450K) in four European and North American studies (n = 1,508) with subsequent look-up analyses in children ages 4 (n = 733) and 8 (n = 786) years. Additionally, we applied a literature-based candidate approach for antioxidant and anti-inflammatory genes. To assess influence of exposure at the transcriptomics level, we related mRNA expression in blood cells to NO2 exposure in 4- (n = 111) and 16-year-olds (n = 239).RESULTS: We found epigenome-wide significant associations [false discovery rate (FDR) p <0.05] between maternal NO2 exposure during pregnancy and DNA methylation in newborns for 3 CpG sites in mitochondria-related genes: cg12283362 (LONP1), cg24172570 (3.8 kbp upstream of HIBADH), and cg08973675 (SLC25A28). The associations with cg08973675 methylation were also significant in the older children. Further analysis of antioxidant and anti-inflammatory genes revealed differentially methylated CpGs in CAT and TPO in newborns (FDR p <0.05). NO2 exposure at the time of biosampling in childhood had a significant impact on CAT and TPO expression.CONCLUSIONS: NO2 exposure during pregnancy was associated with differential offspring DNA methylation in mitochondria-related genes. Exposure to NO2 was also linked to differential methylation as well as expression of genes involved in antioxidant defense pathways.

AB - BACKGROUND: Prenatal exposure to air pollution is considered to be associated with adverse effects on child health. This may partly be mediated by mechanisms related to DNA methylation.OBJECTIVES: We investigated associations between exposure to air pollution, using nitrogen dioxide (NO2) as marker, and epigenome-wide cord blood DNA methylation.METHODS: We meta-analyzed the associations between NO2 exposure at residential addresses during pregnancy and cord blood DNA methylation (Illumina 450K) in four European and North American studies (n = 1,508) with subsequent look-up analyses in children ages 4 (n = 733) and 8 (n = 786) years. Additionally, we applied a literature-based candidate approach for antioxidant and anti-inflammatory genes. To assess influence of exposure at the transcriptomics level, we related mRNA expression in blood cells to NO2 exposure in 4- (n = 111) and 16-year-olds (n = 239).RESULTS: We found epigenome-wide significant associations [false discovery rate (FDR) p <0.05] between maternal NO2 exposure during pregnancy and DNA methylation in newborns for 3 CpG sites in mitochondria-related genes: cg12283362 (LONP1), cg24172570 (3.8 kbp upstream of HIBADH), and cg08973675 (SLC25A28). The associations with cg08973675 methylation were also significant in the older children. Further analysis of antioxidant and anti-inflammatory genes revealed differentially methylated CpGs in CAT and TPO in newborns (FDR p <0.05). NO2 exposure at the time of biosampling in childhood had a significant impact on CAT and TPO expression.CONCLUSIONS: NO2 exposure during pregnancy was associated with differential offspring DNA methylation in mitochondria-related genes. Exposure to NO2 was also linked to differential methylation as well as expression of genes involved in antioxidant defense pathways.

KW - POLYCYCLIC AROMATIC-HYDROCARBONS

KW - DNA METHYLATION

KW - QUANTILE NORMALIZATION

KW - RESPIRATORY HEALTH

KW - OXIDATIVE STRESS

KW - MATERNAL SMOKING

KW - CORD BLOOD

KW - EARLY-LIFE

KW - ASTHMA

KW - ASSOCIATION

U2 - 10.1289/EHP36

DO - 10.1289/EHP36

M3 - Article

VL - 125

SP - 104

EP - 110

JO - Environmental Health Perspectives

JF - Environmental Health Perspectives

SN - 0091-6765

IS - 1

ER -