Maternal circadian disruption is associated with variation in placental DNA methylation.

Danielle A Clarkson-Townsend,Jia Chen,Todd M Everson,Ke Hao,Carmen J Marsit,Karen E Hermetz,Maya A Deyssenroth,Amber A Burt,Henrik Oster

doi:10.1371/journal.pone.0215745

Danielle A Clarkson-Townsend, Jia Chen + Show 7 more

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https://doi.org/10.1371/journal.pone.0215745

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Abstract

Circadian disruption is a common environmental and occupational exposure with public health consequences, but not much is known about whether circadian disruption affects in utero development. We investigated whether maternal circadian disruption, using night shift work as a proxy, is associated with variations in DNA methylation patterns of placental tissue in an epigenome-wide association study (EWAS) of night shift work. Here, we compared cytosine-guanosine dinucleotide (CpG) 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, using robust linear modeling and adjusting for maternal age, pre-pregnancy smoking, infant sex, maternal adversity, and putative cell mixture. Statistical analyses were adjusted for multiple comparisons and results presented with Bonferroni or Benjamini and Hochberg (BH) adjustment for false discovery rate. Night 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). Functional analysis indicated GO-terms associated with cell-cell adhesion and enriched GWAS results for psoriasis. Night shift work was associated with differential methylation of the placenta, which may have implications for fetal health and development. This is the first study to examine the epigenetic impacts of night shift exposure, as a proxy for circadian disruption, on placental methylation in humans, and, while results should be interpreted with caution, suggests circadian disruption may have epigenetic impacts.

Highlights

IntroductionES022832 [to CJM], NIH-NICHD F31 HD097918 [to DACT], and NIH-NIEHS T32 ES012870 [to DACT]) (https://www.nih.gov/) and by the United States Environmental Protection Agency (US EPA grant RD83544201 (https://www.epa.gov/) [to CJM])
We identified a number of CpG sites exhibiting differential methylation associated with night shift work in newborn placental tissue
The overall trend of hypomethylation with night shift work may be due to increased transcription factors (TF) binding to DNA, leading to chromatin changes establishing the hypomethylated state[32]

Summary

Introduction

ES022832 [to CJM], NIH-NICHD F31 HD097918 [to DACT], and NIH-NIEHS T32 ES012870 [to DACT]) (https://www.nih.gov/) and by the United States Environmental Protection Agency (US EPA grant RD83544201 (https://www.epa.gov/) [to CJM]). The study sponsors did not have any role in the study design, collection, analysis, and interpretation of the data, the writing of the report, or the decision to submit the paper for publication

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