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Published on: July 12, 2012
Prenatal black carbon exposure and DNA methylation in umbilical cord blood
Chloe Friedman1, Sierra Niemiec2, Dana Dabelea3
1Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Insights
Prenatal exposure to black carbon (BC) air pollution is linked to altered DNA methylation in newborns. This epigenetic change may partially explain BC
Area of Science:
- Environmental Epigenetics
- Developmental Toxicology
- Cardiometabolic Health
Background:
- Prenatal exposure to ambient air pollution is associated with adverse childhood cardiometabolic outcomes.
- Previous research indicated an inverse association between prenatal black carbon (BC) and childhood adiponectin levels.
- Epigenetic modifications, such as DNA methylation, are hypothesized to mediate the long-term health effects of in utero exposures.
Purpose of the Study:
- To investigate the relationship between prenatal exposure to black carbon (BC) and DNA methylation patterns in cord blood.
- To examine whether DNA methylation mediates the association between prenatal BC exposure and childhood adiponectin levels.
Main Methods:
- Epigenome-wide association study conducted on 532 mother-child pairs from the Colorado Healthy Start study.
- Prenatal ambient BC exposure estimated using a spatiotemporal model at the mother's residence.
- DNA methylation measured in cord blood via Illumina 450K array; multiple linear regression used to assess associations with 429,246 CpGs.
Main Results:
- Forty-four CpG sites were significantly associated with average prenatal ambient BC after multiple testing correction.
- Twenty-four differentially methylated regions (DMRs) were identified by both DMRff and ENmix-combp.
- One CpG site (cg01123250), annotated to the UNC80 gene, was found to mediate approximately 20% of the effect of prenatal BC on childhood adiponectin.
Conclusions:
- Prenatal exposure to black carbon (BC) is associated with significant alterations in cord blood DNA methylation.
- DNA methylation emerges as a potential partial mediator linking prenatal BC exposure to adverse childhood cardiometabolic outcomes.
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.
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