BC Children's Hospital Research Institute and Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Early Hum Dev. 2022 Jan;164:105519. doi: 10.1016/j.earlhumdev.2021.105519. Epub 2021 Nov 29.
Exposure to adverse childhood experiences (ACEs) increases risk for mental and physical health problems. Intergenerationally, mothers' ACEs predict children's health problems including neurodevelopmental and behavioural problems and poorer physical health. Theories of intergenerational trauma suggest that ACEs experienced in one generation negatively affect the health and well-being of future generations, with DNA methylation (DNAm) being one of several potential biological explanations. To begin exploring this hypothesis, we tested whether infant DNA methylation associated with intergenerational trauma. Secondary analysis employed data from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Subsample data were collected from mothers during pregnancy and postpartum on measures of distress, stress and ACEs and from infants at 3 months of age on DNAm from blood (n = 92) and buccal epithelial cells (BECs; n = 124; primarily nonoverlapping individuals between tissues). Blood and BECs were examined in separate analyses. Preliminary associations identified in blood and BECs suggest that infant DNAm patterns may relate to maternal ACEs. For the majority of ACE-related DNAm sites, neither maternal perinatal distress, nor maternal cortisol awakening response (CAR; a measure of hypothalamic-pituitary-adrenocortical axis function), substantially reduced associations between maternal ACEs and infant DNAm. However, accounting for maternal perinatal distress and cortisol substantially changed the effect of ACEs in a greater proportion of blood DNAm sites than BEC DNAm sites in the top ACEs-associated correlated methylated regions (CMRs), as well as across all CMRs and all remaining CpGs (that did not fall into CMRs). Possible DNAm patterns in infants, thus, might capture a signature of maternal intergenerational trauma, and this effect appears to be more dependent on maternal perinatal distress and CAR in blood relative to BECs.
遭受不良的儿童期经历（ACEs）会增加心理健康和身体健康问题的风险。代际间，母亲的 ACEs 可预测儿童的健康问题，包括神经发育和行为问题以及较差的身体健康。代际创伤理论表明，一代人经历的 ACEs 会对后代的健康和幸福产生负面影响，DNA 甲基化（DNAm）是几个潜在的生物学解释之一。为了开始探索这一假设，我们测试了婴儿的 DNA 甲基化是否与代际创伤有关。次级分析采用了艾伯塔省妊娠结局和营养（APrON）研究的数据。从母亲在怀孕期间和产后的压力、压力和 ACE 测量中收集了子样本数据，以及从 3 个月大的婴儿的血液（n=92）和口腔上皮细胞（BEC；n=124；组织间主要是非重叠个体）中收集了 DNAm 数据。分别分析了血液和 BEC。在血液和 BEC 中初步确定的关联表明，婴儿的 DNAm 模式可能与母亲的 ACEs 有关。对于大多数与 ACE 相关的 DNAm 位点，母体围产期压力或母体皮质醇觉醒反应（CAR；下丘脑-垂体-肾上腺皮质轴功能的测量）都没有显著降低母体 ACEs 与婴儿 DNAm 之间的关联。然而，考虑到母体围产期压力和皮质醇，在与 ACEs 相关的关联甲基化区域（CMRs）中，以及在所有 CMRs 和所有剩余的 CpG（不属于 CMRs）中，血液 DNAm 位点中 ACEs 的影响在更大比例上发生了变化，而在 BEC DNAm 位点中则没有。因此，婴儿可能存在 DNAm 模式，可能反映了母体代际创伤的特征，而且这种影响似乎更多地依赖于血液中母体围产期压力和 CAR，而不是 BEC。
