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Your Environment. Your Health.

University of North Carolina-Chapel Hill: Dataset Details, ID=GSE62924

Superfund Research Program

Elucidating Risks: From Exposure and Mechanism to Outcome

Center Director: Rebecca C. Fry
Grant Number: P42ES005948
Funding Period: 1992-2018
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

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Title: Prenatal arsenic exposure and the epigenome: Identifying sites of 5-methyl cytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes

Accession Number: GSE62924

Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62924

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Experiment Type(s): Methylation profiling by array

Organism(s): Homo sapiens

Summary: Prenatal exposure to inorganic arsenic (iAs) is detrimental to the health of newborns and increases the risk of disease development later in life. Here we examined a subset of newborn cord blood leukocyte samples collected from mothers enrolled in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gomez Palacio, Mexico who were exposed to a range of drinking water arsenic concentrations (0.456-236 µg/L). Changes in iAs-associated DNA 5-methyl cytosine methylation were assessed across 424,935 CpG sites representing 18,761 genes and were compared to corresponding expression levels and birth outcomes. In the context of arsenic exposure, a total of 2,705 genes were identified with iAs-associated differences in DNA methylation. Site-specific analyzes identified DNA methylation changes that were most predictive of gene expression levels. Specifically, CpG methylation within CpG islands positioned within the first exon and 200bp upstream of the transcription start site yielded the most significant association with gene expression levels. A set of 16 genes was identified with correlated iAs-associated changes in DNA methylation and mRNA expression and all were highly enriched for binding sites of the early growth response (EGR) and CCCTC-binding factor (CTCF) transcription factors. Furthermore, DNA methylation levels of seven of these genes were associated with differences in birth outcomes including gestational age, placental weight and head circumference. These data highlight the complex interplay between DNA methylation and functional changes in gene expression and health outcomes and underscore the need for functional analyzes coupled to epigenetic assessments.

Publication(s) associated with this dataset:
  • Rojas D, Rager JE, Smeester L, Bailey KA, Drobna Z, Rubio-Andrade M, Styblo M, Garcia-Vargas GG, Fry RC. 2015. Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci 143(1):97-106. doi:10.1093/toxsci/kfu210 PMID:25304211 PMCID:PMC4274382
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