Maternal night shift work is associated with stochastic epigenetic mutations (SEMs) in the placenta Öffentlichkeit

Abstract

Circadian disruption has been associated with many negative health outcomes, such as cognitive impairment, metabolic syndrome, psychiatric illness and also associated with changes in epigenetics, especially DNA methylation. But fewer studies have examined the effects of circadian disruption during pregnancy on maternal and child health. This research was based on 227 mother-infant pairs from the Rhode Island Child Health Study (RICHS). Among the 227 participants, there are 48 women who reported night shift work and 161 women did not. We quantified placental stochastic epigenetic mutations (SEMs) via DNA methylation which was measured with paired Illumina 450K and EPIC microarrays. Using linear regression and Poisson regression we tested the association between night shift work during pregnancy and SEM counts in the placenta.  And we also performed enrichment analysis on the CpGs that had placental SEMs to know whether placental SEMs were enriched in particular biological pathways or were randomly distributed throughout the genome. We found that maternal night shift working had a positive and significant association with SEM counts without covariates (β = 105.18; p=0.01; 95%CI = (21.09, 189.28)) and with covariates, including maternal ethnicity, maternal gravita, delivery method, birthweight group, gender, maternal smoking status and adversity score (β = 107.14; p=0.02; 95%CI = (17.67, 196.60)) via linear regression. Again, with the Poisson regression model, maternal night shift working had a positive and significant association with SEM counts without covariates (β = 0.23; p=0.01; 95%CI = (0.05, 0.41)), and with covariates (β = 0.24; p=0.01; 95%CI = (0.05, 0.42)). We also found that SEMs were more likely to occur in genes that belong to “neuron projection morphogenesis”, “plasma membrane bounded cell projection morphogenesis”, “neuron differentiation”, “cell projection morphogenesis” and “neuron projection development”, “glycosphingolipid biosynthesis - globo and isoglobo series” and “nicotine addiction” pathways. In conclusion, mothers with night shift work tend to have more CpG sites with SEMs than those without nightshift work, with or without controlling for maternal ethnicity, maternal gravita, delivery method, birthweight group, gender, maternal smoking status and adversity score. This demonstrates that SEMs offer an innovative alternative approach to studying the impacts of environmental exposure on placental epigenetics.

Table of Contents

Introduction………………………………………………………………………………1

\Circadian Disruption Impacts Health……………………………………………...…….1

Epigenetic Mechanisms……………………………………………………………….....1

Stochastic Epigenetic Mutations……………………………………………….………..2

Method…………………………………………………………..……………………….3

Study Population………………………………………………………………..…..…...3

Statistical Analyses……………………………………………………...………..……..5

Enrichment Analyses………………………………………………………...………….6

Result…………………………………………………………………………………….6

Study Population Demographics………………………………………………...……....6

Characteristics of SEM counts……………………………………………………...…..7

Higher number SEMs associates with night shift work ………………………..……….7

SEMs are Enriched in Certain Biological Pathways………………………….………....8

Sensitivity Analysis……………………….……………………………….…………….9

Discussion………………………………………………………………………………10

Conclusion and future directions…………………………………………..…....13

Reference…………………………………………………………………………….….14

Table 1………………………………………………………………………………..…17

Figure 1……………………………………………………………………….……..….18

Figure 2……………………………………………………………………………...….19

Table 2……………………………………………………………………………..……20

Table 3……………………………………………………………………………..……21

Table 4……………………………………………………………………………..……22

About this Master's Thesis

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School	Rollins School of Public Health
Department	Environmental Health
Degree	M.S.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health Health Sciences, Epidemiology Environmental Health
Stichwort	stochastic epigenetic mutations (SEMs) circadian disruption night shift
Committee Chair / Thesis Advisor	Todd Everson, Emory University

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