Prenatal maternal stress is associated with site-specific and age acceleration changes in maternal and newborn DNA methylation

Abstract

Prenatal maternal stress has a negative impact on child health but the mechanisms through which maternal stress affects child health are unclear. Epigenetic variation, such as DNA methylation, is a likely mechanistic candidate as DNA methylation is sensitive to environmental insults and can regulate long-term changes in gene expression. We recruited 155 mother-newborn dyads in the Democratic Republic of Congo to investigate the effects of maternal stress on DNA methylation in mothers and newborns. We used four measures of maternal stress to capture a range of stressful experiences: general trauma, sexual trauma, war trauma, and chronic stress. We identified differentially methylated positions (DMPs) associated with general trauma, sexual trauma, and war trauma in both mothers and newborns. No DMPs were associated with chronic stress. Sexual trauma was positively associated with epigenetic age acceleration across several epigenetic clocks in mothers. General trauma and war trauma were positively associated with newborn epigenetic age acceleration using the extrinsic epigenetic age clock. We tested the top DMPs for enrichment of DNase I hypersensitive sites (DHS) and found no enrichment in mothers. In newborns, top DMPs associated with war trauma were enriched for DHS in embryonic and foetal cell types. Finally, one of the top DMPs associated with war trauma in newborns also predicted birthweight, completing the cycle from maternal stress to DNA methylation to newborn health outcome. Our results indicate that maternal stress is associated with site-specific changes in DNAm and epigenetic age acceleration in both mothers and newborns.

Non-coding 886 ( nc886 / vtRNA2-1 ), the epigenetic odd duck – implications for future studies

“…All new analyses performed have utilized data that are freely available or available upon reasonable request. For different geographic origins, data from Khomeni San (GSE99029 [ 64 ], Gambian (GSE99863 [ 118 ], Malawian and Jamaican (GSE112893 [ 119 ], African American (GSE210255 [ 120 ], Multiethnic American (GSE36369 [ 65 ], Central African ( https://ega-archive.org/EGAD00010000692 ; [ 66 ], Gambian (GSE59592 [ 13 ], Congolese (GSE224363 [ 121 ], Latin American (GSE77716 [ 122 ], individuals of European ancestry (summary statistics [ 6 ], Bangladeshi ( http://datadryad.org/10.5061/dryad.k67kf [ 14 ], Chinese (GSE116379 [ 78 ] Han Chinese (GSE201287 [ 123 ], Taiwanese (GSE78904 [ 124 ] and Indonesian ( https://figshare.com,10.26188/5e00abd72f581 , [ 67 ] cohorts were utilized. In the reanalyses and attempts to replicate previous associations of nc886 methylation pattern and phenotypes, the following datasets were used: GSE52576 [ 57 ] for parthenogenetically activated oocytes and embryonic stem cells; GSE59592 and GSE99863 for season of conception; http://datadryad.org/10.5061/dryad.k67kf , and GSE116379 for postnatal and prenatal exposure to famine; and GSE165081 [ 81 ], GSE145361 [ 83 ] and GSE111629 [ 125 ] for the presence of Parkinson’s disease.…”

Map of epigenetic age acceleration: a worldwide meta-analysis

“…There are 2 datasets (190 samples, 3-42 years) for this country. The larger dataset (177) contains only women who have recently given birth [61], the smaller dataset contains 3-year-olds [62]. South Korea has an Aggregated Sign of <EAA> value of -6 (there are 6 more epigenetic estimates showing decelerated aging than epigenetic estimates showing accelerated aging).…”

Non-coding 886 (nc886/vtRNA2-1), the epigenetic odd duck – implications for future studies

“…The DNA methylation pattern in the nc886 locus should be treated as a binomial variable to avoid reporting false positive findings due to the random distribution of nonmethylated and imprinted individuals in cases and controls. Multi-ethnic American (GSE36369 63 ), Central African (https://ega-archive.org/; EGAD00010000692 64 ), Gambian (GSE59592 13 ), Congolese (GSE224363 119 ), Latin American (GSE77716 120 ), Caucasian (summary statistics 6 ), Bangladeshi (http://datadryad.org/, doi:10.5061/dryad.k67kf 14 ), Chinese (GSE116379 76 ) Han Chinese (GSE201287 121 ), Taiwanese (GSE78904 122 ) and Indonesian (https://figshare.com, 10.26188/5e00abd72f581 65 ) cohorts were utilized. Re-analysing and attempting to replicate previous associations of nc886 methylation pattern and phenotypes, the follow data seta were used; parthenogenetically activated oocytes and embryonic stem cells (GSE52576 55 ); for season of conception GSE59592 and GSE99863; for postnatal and prenatal exposure to famine (http://datadryad.org/, doi:10.5061/dryad.k67kf) and GSE116379 and for the presence of Parkinson's disease (GSE165081 79 , GSE145361 81 and GSE111629 123 ).…”