Biology subjects

Everson, T. M.

Publications and source records attributed to Everson, T. M..

2 recordsLinked to original sources

bioRxiv2018

Epigenome-wide association study of placental DNA methylation and maternal exposure to night shift work in the Rhode Island Child Health Study

ObjectivesCircadian disruption from environmental and occupational exposures can potentially impact health, including offspring health, through epigenetic alterations. Night shift workers experience circadian disruption, but little is known about how this exposure could influence the epigenome of the placenta, which is situated at the maternal-fetal interface. To investigate whether night shift work is associated with variations in DNA methylation patterns of placental tissue, we conducted an epigenome-wide association study (EWAS) of night shift work.\n\nMethodsCpG specific methylation genome-wide of placental tissue (measured with the Illumina 450K array) from participants (n=237) in the Rhode Island Child Health Study (RICHS) who did (n=53) and did not (n=184) report working the night shift was compared using robust linear modeling, adjusting for maternal age, pre-pregnancy smoking, infant sex, maternal adversity, and putative cell mixture.\n\nResultsNight shift work was associated with differential methylation in placental tissue, including CpG sites in the genes NAV1, SMPD1, TAPBP, CLEC16A, DIP2C, FAM172A, and PLEKHG6 (Bonferroni-adjusted p<0.05). CpG sites within NAV1, MXRA8, GABRG1, PRDM16, WNT5A, and FOXG1 exhibited the most hypomethylation, while CpG sites within TDO2, ADAMTSL3, DLX2, and SERPINA1 exhibited the most hypermethylation (BH q<0.10). PER1 was the only core circadian gene demonstrating differential methylation. Functional analysis indicated GO-terms associated with cell-cell adhesion.\n\nConclusionsNight shift work was associated with differential methylation of the placenta, which may have implications for fetal health and development. Additionally, neuron navigator 1 (NAV1) may play a role in the development of the human circadian system.\n\nWhat is already known about this subject?Night shift work and circadian disruption may play a role in the development and progression of many diseases. However, little is known about how circadian disruption impacts human fetal health and development.\n\nWhat are the new findings?Working the night shift is associated with altered placental methylation patterns, and particularly, neuron navigator 1 (NAV1) may play a role in the development of the human circadian system.\n\nHow might this impact on policy or clinical practice in the foreseeable future?Night shift work prior to or during pregnancy may alter the placental epigenome, which has implications for fetal health. Further studies are needed to evaluate night shift work as a possible risk factor for gestational diabetes and to evaluate the impact of circadian disruption on fetal health and development.

epidemiology↗

bioRxiv2017

Cadmium-associated differential methylation throughout the placental genome: epigenome-wide association study of two US birth cohorts

BackgroundCadmium (Cd) is a ubiquitous toxicant that during pregnancy can impair fetal development. Cd sequesters in the placenta where it can impair placental function, impacting fetal development. We aimed to investigate Cd-associated variations in placental DNA methylation (DNAM), associations with gene expression, and identify novel pathways involved in Cd-associated reproductive toxicity.\n\nMethodsUsing placental DNAM and Cd concentrations in the New Hampshire Birth Cohort Study (NHBCS, n=343) and the Rhode Island Child Health Study (RICHS, n=141), we performed an EWAS between Cd and DNAM, adjusting for tissue heterogeneity using a reference-free method. Cohort-specific results were aggregated via inverse variance weighted fixed effects meta-analysis, and variably methylated CpGs were associated with gene expression. We then performed functional enrichment analysis and tests for associations between gene expression and birth metrics.\n\nResultsWe identified 17 Cd-associated differentially methylated CpG sites with meta-analysis p-values < 1e-05, two of which were within a 5% false discovery rate (FDR). Methylation levels at 9 of the 17 loci were associated with increased expression of 6 genes (5% FDR): TNFAIP2, EXOC3L4, GAS7, SREBF1, ACOT7, and RORA. Higher placental expression of TNFAIP2 and ACOT7, and lower expression of RORA, were associated with lower birth weight z-scores (p-values < 0.05).\n\nConclusionCd associated differential DNAM and corresponding DNAM-expression associations at these loci are involved in inflammatory signaling and cell growth. The expression levels of genes involved in inflammatory signaling (TNFAIP2, ACOT7, and RORA), were also associated with birth metrics, suggesting a role for inflammatory processes in Cd-associated reproductive toxicity.\n\nSignificanceCadmium is a toxic environmental pollutant that can impair fetal development. The mechanisms underlying this toxicity are unclear, though disrupted placental functions could play an important role. In this study we examined associations between cadmium concentrations and DNA methylation throughout the placental genome, across two US birth cohorts. We observed cadmium-associated differential methylation, and corresponding methylation-expression associations at genes involved in cellular growth processes and/or immune and inflammatory signaling. This study provides supporting evidence that disrupted placental epigenetic regulation of cellular growth and immune/inflammatory signaling could play a role in cadmium associated reproductive toxicity in human pregnancies.

epidemiology↗