Methylation quantitative trait loci analysis in Korean exposome study

Zinia

et al. 2023

Sci Rep

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Exposure to phthalates has been shown to impede the human endocrine system, resulting in deleterious effects on pregnant women and their children. Phthalates modify DNA methylation patterns in infant cord blood. We examined the association between prenatal phthalate exposure and DNA methylation patterns in cord blood in a Korean birth cohort. Phthalate levels were measured in 274 maternal urine samples obtained during late pregnancy and 102 neonatal urine samples obtained at birth, and DNA methylation levels were measured in cord blood samples. For each infant in the cohort, associations between CpG methylation and both maternal and neonate phthalate levels were analyzed using linear mixed models. The results were combined with those from a meta-analysis of the levels of phthalates in maternal and neonatal urine samples, which were also analyzed for MEOHP, MEHHP, MnBP, and DEHP. This meta-analysis revealed significant associations between the methylation levels of CpG sites near the CHN2 and CUL3 genes, which were also associated with MEOHP and MnBP in neonatal urine. When the data were stratified by the sex of the infant, MnBP concentration was found to be associated with one CpG site near the OR2A2 and MEGF11 genes in female infants. In contrast, the concentrations of the three maternal phthalates showed no significant association with CpG site methylation. Furthermore, the data identified distinct differentially methylated regions in maternal and neonatal urine samples following exposure to phthalates. The CpGs with methylation levels that were positively associated with phthalate levels (particularly MEOHP and MnBP) were found to be enriched genes and related pathways. These results indicate that prenatal phthalate exposure is significantly associated with DNA methylation at multiple CpG sites. These alterations in DNA methylation may serve as biomarkers of maternal exposure to phthalates in infants and are potential candidates for investigating the mechanisms by which phthalates impact maternal and neonatal health.

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Prenatal phthalate exposure and cord blood DNA methylation

Joo-Ah

Zinia

et al. 2023

Sci Rep

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“…The methylation levels of the cord blood samples were determined using Illumina HumanMethylationEPIC BeadChip with the manufacturer’s instructions. Genotyping of the samples was performed as previously described [ 19 ]. Briefly, cord blood samples were genotyped on Asian Precision Medicine Research Array (APMRA; Affymetrix, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Prenatal Exposure to Traffic-Related Air Pollution and the DNA Methylation in Cord Blood Cells: MOCEH Study

Park

et al. 2022

IJERPH

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Particulate matter with a diameter of ≤10 µm (PM10) and nitrogen dioxide (NO2) affect the DNA methylation in the fetus, but epigenetic studies regarding prenatal exposure to air pollution in Asia are lacking. Therefore, this study aimed to assess whether there is any association between the ambient concentrations of PM10 and NO2 and CpG methylation in the cord blood DNA by using a Korean birth cohort. The concentrations of the air pollutants were incorporated into the final LUR model by using the maternal address data. The methylation level was determined using HumanMethylationEPIC BeadChip and a linear regression analysis model. A multipollutant model including both PM10 and NO2 and models with single pollutants were used for each trimester exposure. The number of differentially methylated positions was the largest for midpregnancy exposure in both the single pollutant models and the multipollutant regression analysis. Additionally, gene-set analysis regarding midpregnancy exposure revealed four gene ontology terms (cellular response to staurosporine, positive regulation of cytoskeleton organization, neurotransmitter transport, and execution phase of apoptosis). In conclusion, these findings show an association between prenatal PM10 and NO2 exposure and DNA methylation in several CpG sites in cord blood cells, especially for midpregnancy exposure.

“…DNA methylation level was measured from the blood samples, following the instructions of the Illumina HumanMethylationEPIC BeadChip kit (Illumina, California) and methods from the Korean Exposome Study [20,21] . The measured data were preprocessed following the recommended quality control (QC) work ow of the 'ewastools' package in R [22,23] .…”

Section: Dna Methylation Data Preprocessingmentioning

confidence: 99%

Prenatal phthalate exposure and cord blood DNA methylation

Joo-Ah

Zinia

et al. 2022

Preprint

Self Cite

The indiscriminate use of phthalate-containing products in daily life can adversely affect pregnant women and their children. Phthalate can modify DNA methylation in the cord blood of infants. Therefore, we examined the association between prenatal phthalate exposure and cord blood DNA methylation in a Korean birth cohort. Phthalate levels in maternal blood during late pregnancy and cord blood were measured and DNA methylation of cord blood was measured using the Illumina HumanMethylationEPIC BeadChip kit. The association between CpG methylation and phthalate levels was analyzed using the ‘limma’ package in R, adjusting for infant sex, maternal body mass index, current maternal smoking status, and estimated leukocyte composition. We used data from 274 samples for estimating mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono-(2-ethyl-5-hydroxyhxyl) phthalate (MEHHP) levels and 273 samples for estimating mono-n-butyl phthalate (MnBP) levels to determine maternal phthalate concentrations during late pregnancy. Additionally, 102 samples were analyzed for all three types of phthalates in the cord blood. The meta-analysis revealed significant associations between the CpG sites near the CHN2 and CUL3 genes and cord blood MEOHP and MnBP concentrations, respectively. However, the three maternal phthalate concentrations during late pregnancy showed no significant association with CpG sites. In conclusion, prenatal phthalate exposure is significantly associated with DNA methylation at several CpG sites.