@article{9ea3d04129614e50be4a9200752b0236,
title = "Prenatal black carbon exposure and DNA methylation in umbilical cord blood",
abstract = "Background/objectives: Prenatal exposure to ambient air pollution is associated with adverse cardiometabolic outcomes in childhood. We previously observed that prenatal black carbon (BC) was inversely associated with adiponectin, a hormone secreted by adipocytes, in early childhood. Changes to DNA methylation have been proposed as a potential mediator linking in utero exposures to lasting health impacts. Methods: Among 532 mother-child pairs enrolled in the Colorado-based Healthy Start study, we performed an epigenome-wide association study of the relationship between prenatal exposure to a component of air pollution, BC, and DNA methylation in cord blood. Average pregnancy ambient BC was estimated at the mother's residence using a spatiotemporal prediction model. DNA methylation was measured using the Illumina 450K array. We used multiple linear regression to estimate associations between prenatal ambient BC and 429,246 cysteine-phosphate-guanine sites (CpGs), adjusting for potential confounders. We identified differentially methylated regions (DMRs) using DMRff and ENmix-combp. In a subset of participants (n = 243), we investigated DNA methylation as a potential mediator of the association between prenatal ambient BC and lower adiponectin in childhood. Results: We identified 44 CpGs associated with average prenatal ambient BC after correcting for multiple testing. Several genes annotated to the top CpGs had reported functions in the immune system. There were 24 DMRs identified by both DMRff and ENmix-combp. One CpG (cg01123250), located on chromosome 2 and annotated to the UNC80 gene, was found to mediate approximately 20% of the effect of prenatal BC on childhood adiponectin, though the confidence interval was wide (95% CI: 3, 84). Conclusions: Prenatal BC was associated with DNA methylation in cord blood at several sites and regions in the genome. DNA methylation may partially mediate associations between prenatal BC and childhood cardiometabolic outcomes.",
keywords = "Air pollution, Cord blood, DNA methylation, Prenatal exposure",
author = "Chloe Friedman and Sierra Niemiec and Dana Dabelea and Katerina Kechris and Yang, {Ivana V.} and Adgate, {John L.} and Glueck, {Deborah H.} and Martenies, {Sheena E.} and Sheryl Magzamen and Starling, {Anne P.}",
note = "This work was supported in part by grants from the National Institute of Environmental Health Sciences (F31ES034938, R01ES022934), the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK076648), and the National Institutes of Health Office of the Director (UH3OD023248). The University of Colorado Clinical and Translational Sciences Institute Core Laboratories received support from the National Center for Advancing Translational Sciences (UL1TR001082). Funders had no involvement in the data collection, analysis, or interpretation of results, and were not involved in the writing of the article or the decision to submit the article for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Existing epidemiologic evidence, including a publication from our group, (Starling et al., 2022) supports associations between prenatal exposure to PM2.5 and close proximity to roadways and alterations in DNA methylation in placental tissue and cord blood, (Ferrari et al., 2019) infant saliva, (Parikh et al., 2022) newborn blood spots (Breton et al., 2016). In a meta-analysis of epigenome-wide association studies (EWAS) of data from 9 European and American studies, Gruzieva et al. found 14 cysteine-phosphate-guanine (CpG) sites in cord blood to be significantly associated with prenatal PM2.5 (Gruzieva et al., 2019). Some prior studies have also explored whether the prenatal PM2.5-associated differential methylation explained observed associations with birth, growth, and cardiometabolic health outcomes for the offspring, though results have been inconsistent (Starling et al., 2022; Breton et al., 2016; Wang et al., 2020; Liu et al., 2019; Cho et al., 2021).Among the few prior studies investigating the relationships between prenatal PM2.5, DNA methylation at birth, and birth, growth, and cardiometabolic health of the offspring, (Starling et al., 2022; Breton et al., 2016; Wang et al., 2020; Liu et al., 2019; Cho et al., 2021) only two have studied outcomes beyond infancy, and results were inconsistent (Breton et al., 2016; Cho et al., 2021). While there is a lack of existing literature in humans on this topic, evidence from animal studies supports alterations to epigenetic mechanisms as a potential biological explanation for observed associations (Chen et al., 2017; Goodson et al., 2019; Tanwar et al., 2017). For example, Chen et al. found among male, but not female, offspring mice, prenatal PM2.5 exposure was associated with greater adiposity, decreased expression of leptin, a critical hormone for energy homeostasis, and increased DNA methylation at a site in the promoter region of the leptin gene in adipocytes (Chen et al., 2017).This work was supported in part by grants from the National Institute of Environmental Health Sciences (F31ES034938, R01ES022934), the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK076648), and the National Institutes of Health Office of the Director (UH3OD023248). The University of Colorado Clinical and Translational Sciences Institute Core Laboratories received support from the National Center for Advancing Translational Sciences (UL1TR001082). Funders had no involvement in the data collection, analysis, or interpretation of results, and were not involved in the writing of the article or the decision to submit the article for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.",
year = "2025",
month = jan,
doi = "10.1016/j.ijheh.2024.114464",
language = "English (US)",
volume = "263",
journal = "International Journal of Hygiene and Environmental Health",
issn = "1438-4639",
publisher = "Elsevier GmbH",
}