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

作者：Edward B. Quinn, Chu Hsiao, Felicien Maisha, Connie J. Mulligan · 发表于：Epigenetics · 年份：2023 · DOI：10.1080/15592294.2023.2222473 · 被引用次数：27 · 研究领域：Epigenetics and DNA Methylation、Birth, Development, and Health、Family Support in Illness

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 ou...