Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, New York.
Department of Psychiatry, Columbia University, New York, New York.
JAMA Netw Open. 2024 Aug 1;7(8):e2427063. doi: 10.1001/jamanetworkopen.2024.27063.
Adverse childhood experiences (ACEs), potentially traumatic experiences occurring before the age of 18 years, are associated with epigenetic aging later in life and may be transmitted across generations.
To test evidence of the transmission of biological embedding of life experience across generations by analyzing maternal ACEs and epigenetic clocks measured in mothers during pregnancy and in their children at birth.
DESIGN, SETTING, AND PARTICIPANTS: For this cross-sectional study, data from the Accessible Resource for Integrated Epigenomic Studies (ARIES) substudy of the Avon Longitudinal Study of Parents and Children (ALSPAC) were analyzed. The ALSPAC study recruited 14 541 women who gave birth in the Avon Health District in the UK between April 1, 1991, and December 31, 1992. The ARIES substudy comprised 1018 mother-offspring dyads based on the availability of DNA samples profiled in 2014. Epigenetic age was estimated using DNA methylation-based epigenetic clocks (including Horvath, Hannum, GrimAge, PhenoAge, and DunedinPACE) in mothers during pregnancy and the Knight and Bohlin cord blood epigenetic clocks in newborns. Analyses were performed between October 1, 2022, and November 30, 2023.
A composite measure of maternal ACEs was the primary exposure in both maternal and offspring models; as a secondary analysis, individual ACEs were measured separately. The Edinburgh Postnatal Depression Scale (EPDS) was used to investigate depression during pregnancy as an exposure.
Changes in epigenetic age acceleration (EAA) were investigated as the primary outcome in maternal models during pregnancy. Changes in epigenetic gestational age acceleration (GAA) were the primary outcome in offspring analyses. Linear regression analyses were used to determine the association between maternal ACEs and both outcomes.
This study included 883 mother-child dyads. The mean (SD) maternal age at delivery was 29.8 (4.3) years. Pregnant women with higher ACE scores exhibited higher GrimAge EAA (β, 0.22 [95% CI, 0.12 to 0.33] years; P < .001). Maternal ACEs were not associated with GAA in newborns using P < .05 as a cutoff to determine statistical significance. Depression was associated with higher GrimAge EAA (β, 0.06 [95% CI, 0.02 to 0.10] years; P = .01) in mothers during pregnancy, but not in newborns, and did not mediate the association between ACEs and EAA.
The findings of this study suggest that maternal ACEs may be associated with epigenetic aging later in life, including during pregnancy, supporting a role for maternal ACEs in offspring development and health later in life.
发生在 18 岁之前的不良童年经历（ACEs）是潜在的创伤性经历，与晚年的表观遗传衰老有关，并且可能在代际间传播。
通过分析怀孕期间母亲的 ACEs 和表观遗传时钟，以及在出生时母亲的孩子的表观遗传时钟，来测试生活经历的生物学嵌入在代际间传递的证据。
设计、地点和参与者：这项横断面研究分析了可访问资源综合表观基因组学研究（ARIES）子研究的数据集，该研究是英国阿冯纵向父母与子女研究（ALSPAC）的一部分。ALSPAC 研究招募了 1991 年 4 月 1 日至 1992 年 12 月 31 日期间在英国阿冯卫生区分娩的 14541 名女性。ARIES 子研究基于 2014 年可用的 DNA 样本，包括 1018 对母婴对子。在怀孕期间使用基于 DNA 甲基化的表观遗传时钟（包括 Horvath、Hannum、GrimAge、PhenoAge 和 DunedinPACE）和新生儿 Knight 和 Bohlin 脐带血表观遗传时钟来估计表观遗传年龄。分析于 2022 年 10 月 1 日至 2023 年 11 月 30 日之间进行。
母亲的 ACEs 综合衡量是母亲和后代模型中的主要暴露因素；作为二次分析，单独测量了个体 ACEs。爱丁堡产后抑郁量表（EPDS）用于调查怀孕期间的抑郁作为暴露因素。
作为主要结果，在怀孕期间的母亲模型中，我们研究了表观遗传年龄加速（EAA）的变化。在后代分析中，表观遗传孕龄加速（GAA）的变化是主要结果。线性回归分析用于确定母亲 ACEs 与这两个结果之间的关联。
本研究包括 883 对母婴对子。孕妇的平均（SD）分娩年龄为 29.8（4.3）岁。具有较高 ACE 评分的孕妇表现出较高的 GrimAge EAA（β，0.22 [95%CI，0.12 至 0.33] 年；P < 0.001）。在使用 P < 0.05 作为确定统计学意义的截止值时，母亲 ACEs 与新生儿的 GAA 没有关联。怀孕期间，抑郁与母亲更高的 GrimAge EAA（β，0.06 [95%CI，0.02 至 0.10] 年；P = 0.01）相关，但与新生儿无关，且不能介导 ACEs 与 EAA 之间的关联。
这项研究的结果表明，母亲的 ACEs 可能与晚年的表观遗传衰老有关，包括怀孕期间，这支持了 ACEs 在后代发育和晚年健康中的作用。
