Dataset Information

Prenatal Exposure to Cadmium and Cotinine and CpG island DNA methylation in Mother-Infant Pairs.

ABSTRACT: A precise biological mechanism by which cadmium acts as a developmental toxicant is unknown but is suggested to include an epigenetic basis. In prior work, we analyzed CpG island methylation levels within gene promoters (n=16,421) in leukocytes collected from mothers and their infants from a pregnancy cohort in Durham County, North Carolina. The CpG methylation levels were examined in relationship to prenatal exposure to cadmium and/or cotinine to identify genes and pathways influenced by in utero exposure. In the present article, we provide an enhanced description of the data collection and processing to facilitate cross-study comparisons. Data are available within the Gene Expression Omnibus database (GSE67976).

SUBMITTER: Gona S

PROVIDER: S-EPMC4538703 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Prenatal Exposure to Cadmium and Cotinine and CpG island DNA methylation in Mother-Infant Pairs.

Gona Saideep S Sanders Alison P AP Miranda Marie Lynn ML Fry Rebecca C RC

Genomics data 20150901

A precise biological mechanism by which cadmium acts as a developmental toxicant is unknown but is suggested to include an epigenetic basis. In prior work, we analyzed CpG island methylation levels within gene promoters (n=16,421) in leukocytes collected from mothers and their infants from a pregnancy cohort in Durham County, North Carolina. The CpG methylation levels were examined in relationship to prenatal exposure to cadmium and/or cotinine to identify genes and pathways influenced by <i>in< ...[more]

PMID: 26295018

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Project description:BackgroundPer- and polyfluoroalkyl substances (PFAS) are chemicals that are resistant to degradation and ubiquitous in our environments. PFAS may impact the developing epigenome, but current human evidence is limited to assessments of total DNA methylation. We assessed associations between first trimester PFAS exposures with newborn DNA methylation, including 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC). DNA methylation mediation of associations between PFAS and birth outcomes were explored in the Michigan Mother Infant Pairs cohort. Nine PFAS were measured in maternal first trimester blood. Seven were highly detected and included for analysis: PFHxS, PFOA, PFOS, PFNA, PFDA, PFUnDA, and MeFOSAA. Bisulfite-converted cord blood DNA (n = 141) and oxidative-bisulfite-converted cord blood (n = 70) were assayed on Illumina MethylationEPIC BeadChips to measure total DNA methylation (5-mC + 5-hmC) and 5-mC/5-hmC. Correcting for multiple comparisons, beta regressions were used to assess associations between levels of PFAS and total methylation, 5-mC, or 5-hmC. Nonlinear mediation analyses were used to assess the epigenetic meditation effect between PFAS and birth outcomes.ResultsPFAS was significantly associated with total methylation (q < 0.05: PFHxS-12 sites; PFOS-19 sites; PFOA-2 sites; PFNA-3 sites; PFDA-4 sites). In 72 female infants and 69 male infants, there were sex-specific associations between five PFAS and DNA methylation. 5-mC and 5-hmC were each significantly associated with thousands of sites for PFHxS, PFOS, PFNA, PFDA, PFUnDA, and MeFOSAA (q < 0.05). Clusters of 5-mC and 5-hmC sites were significant mediators between PFNA and PFUnDA and decreased gestational age (q < 0.05).ConclusionsThis study demonstrates the mediation role of specific types of DNA methylation on the relationship between PFAS exposure and birth outcomes. These results suggest that 5-mC and 5-hmC may be more sensitive to the developmental impacts of PFAS than total DNA methylation.

Dataset Information

Prenatal Exposure to Cadmium and Cotinine and CpG island DNA methylation in Mother-Infant Pairs.

Publications

Prenatal Exposure to Cadmium and Cotinine and CpG island DNA methylation in Mother-Infant Pairs.

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