BACKGROUND Epigenetic mechanisms may partly explain the persistent effects of adverse childhood experiences (ACEs) on health outcomes in later life. DNA methylation can predict chronological age, and advanced methylation-predicted age beyond chronological age (DNA methylation age acceleration) is associated with ACEs, adverse mental and physical health, and elevated diurnal and baseline salivary cortisol. Childhood adversity is also associated with dysregulation of the hypothalamic-pituitary-adrenal axis, which produces the neuroendocrine hormone cortisol. It remains unknown whether these associations are specific to certain types of adversity. Herein, we investigate the associations of ACEs with DNA methylation age acceleration and plasma cortisol in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. METHODS In this study of the children in ALSPAC, we used multiple linear regression to examine associations of cumulative exposure to ACE, as well as exposure to ten individual types of ACEs, with Horvath-estimated DNA methylation age acceleration and with baseline plasma cortisol. The ten ACEs were those included in the World Health Organization's ACE International Questionnaire. Data on ACEs were prospectively collected from age 0-14 years. DNA methylation age acceleration and plasma cortisol were measured at mean 17.1 years and 15.5 years, respectively. RESULTS We included 974 UK children in the present study. Exposure to four or more ACEs compared to zero was associated with DNA methylation age acceleration in girls (β, 95% CI = 1.65, 0.25 to 3.04 years) but not in boys (β, 95% CI = - 0.11, - 1.48 to 1.26 years). Also, in girls, emotional abuse and physical abuse were each associated with DNA methylation age acceleration (β, 95% CI = 1.20, 0.15 to 2.26 years and β, 95% CI = 1.22, 0.06 to 2.38 years, respectively). No other ACEs were associated with accelerated DNA methylation age in either sex. Associations were also null between ACE and cortisol, and cortisol and DNA methylation age acceleration. CONCLUSIONS In this prospective population-based study of UK children, cumulative ACE exposure, emotional abuse, and physical abuse between age 0 and 14 years were each associated with Horvath-estimated DNA methylation age acceleration at age 17 years in girls but not in boys.

中文翻译：

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英国儿童的不良童年经历、DNA 甲基化年龄加速和皮质醇：一项基于人群的前瞻性队列研究。

背景 表观遗传机制可以部分解释不良童年经历 (ACE) 对晚年健康结果的持续影响。DNA 甲基化可以预测实际年龄，超过实际年龄的晚期甲基化预测年龄（DNA 甲基化年龄加速）与 ACE、不利的身心健康以及昼夜和基线唾液皮质醇升高有关。童年逆境也与下丘脑-垂体-肾上腺轴的失调有关，该轴产生神经内分泌激素皮质醇。目前尚不清楚这些关联是否特定于某些类型的逆境。在此，我们在雅芳父母和儿童纵向研究 (ALSPAC) 出生队列中研究了 ACE 与 DNA 甲基化年龄加速和血浆皮质醇的关系。方法 在这项针对 ALSPAC 的儿童的研究中，我们使用多元线性回归来检查累积暴露于 ACE 以及暴露于 10 种单独类型的 ACE、Horvath 估计的 DNA 甲基化年龄加速和基线血浆皮质醇之间的关联。这十个 ACE 是世界卫生组织的 ACE 国际问卷中包含的那些。ACE 的数据是从 0-14 岁前瞻性收集的。DNA 甲基化年龄加速和血浆皮质醇的平均测量时间分别为 17.1 岁和 15.5 岁。结果 我们在本研究中纳入了 974 名英国儿童。与零相比，暴露于四种或更多 ACE 与女孩 DNA 甲基化年龄加速相关（β，95% CI = 1.65，0.25 至 3.04 岁），但与男孩无关（β，95% CI = - 0.11， - 1.48 至 1.26年）。此外，在女孩中，情感虐待和身体虐待均与 DNA 甲基化年龄加速相关（β，95% CI = 1.20, 0.15 至 2.26 岁和 β, 95% CI = 1.22, 0.06 至 2.38 岁）。在任何性别中，没有其他 ACE 与加速的 DNA 甲基化年龄相关。ACE 和皮质醇以及皮质醇和 DNA 甲基化年龄加速之间的关联也为零。结论 在这项针对英国儿童的前瞻性基于人群的研究中，0 至 14 岁之间的累积 ACE 暴露、情感虐待和身体虐待均与 Horvath 估计的女孩 17 岁时 DNA 甲基化年龄加速相关，但与男孩无关。在任何性别中，没有其他 ACE 与加速的 DNA 甲基化年龄相关。ACE 和皮质醇以及皮质醇和 DNA 甲基化年龄加速之间的关联也为零。结论 在这项针对英国儿童的前瞻性基于人群的研究中，0 至 14 岁之间的累积 ACE 暴露、情感虐待和身体虐待均与 Horvath 估计的女孩 17 岁时 DNA 甲基化年龄加速相关，但与男孩无关。在任何性别中，没有其他 ACE 与加速的 DNA 甲基化年龄相关。ACE 和皮质醇以及皮质醇和 DNA 甲基化年龄加速之间的关联也为零。结论 在这项针对英国儿童的前瞻性基于人群的研究中，0 至 14 岁之间的累积 ACE 暴露、情感虐待和身体虐待均与 Horvath 估计的女孩 17 岁时 DNA 甲基化年龄加速相关，但与男孩无关。