Cumulative lifetime maternal stress and epigenome-wide placental DNA methylation in the PRISM cohort.

Epigenetics : Official Journal of the DNA Methylation Society
Kelly J BrunstRosalind J Wright

Abstract

Evolving evidence links maternal stress exposure to changes in placental DNA methylation of specific genes regulating placental function that may have implications for the programming of a host of chronic disorders. Few studies have implemented an epigenome-wide approach. Using the Infinium HumanMethylation450 BeadChip (450K), we investigated epigenome-wide placental DNA methylation in relation to maternal experiences of traumatic and non-traumatic stressors over her lifetime assessed using the Life Stressor Checklist-Revised (LSC-R) survey (n = 207). We found differential DNA methylation at epigenome-wide statistical significance (FDR = 0.05) for 112 CpGs. Additionally, we observed three clusters that exhibited differential methylation in response to high maternal lifetime stress. Enrichment analyses, conducted at an FDR = 0.20, revealed lysine degradation to be the most significant pathway associated with maternal lifetimes stress exposure. Targeted enrichment analyses of the three largest clusters of probes, identified using the gap statistic, were enriched for genes associated with endocytosis (i.e., SMAP1, ANKFY1), tight junctions (i.e., EPB41L4B), and metabolic pathways (i.e., INPP5E, EEF1B2). These pathways, also identif...Continue Reading

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Citations

Dec 4, 2020·Physiological Reviews·Daniel J HoffmanDaniel B Hardy
Dec 18, 2020·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Xi-Meng WangWei-Qing Chen
Jan 24, 2021·Clinical Therapeutics·Nana MatobaJames W Collins
Feb 25, 2021·European Journal of Preventive Cardiology·James M MuchiraLaura L Hayman
May 29, 2021·Biology of Sex Differences·Amy M InksterWendy P Robinson
Jun 23, 2021·Human Molecular Genetics·Suvo ChatterjeeFasil Tekola-Ayele

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Methods Mentioned

BETA
GAM
Assay
chips
methylation profiling

Software Mentioned

R package wateRmelon
ReFACTor
R
Bioconductor ‘ missMethyl ’ R
PRISM
gam

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