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 -