Sensitive Periods for the Effect of Childhood Adversity on DNA Methylation: Results From a Prospective, Longitudinal Study
Sensitive Periods for the Effect of Childhood Adversity on DNA Methylation: Results From a Prospective, Longitudinal Study
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DOI：
10.1016/j.biopsych.2018.12.023
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发表时间：
2019-05-15
影响因子：
10.6
通讯作者：
Relton, Caroline L.
中科院分区：
文献类型：
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作者：
Dunn, Erin C.;Soare, Thomas W.;Relton, Caroline L.
背景：已知暴露于早期生活逆境可以预测可能与精神病风险相关的DNA甲基化（DNAm）模式。然而，很少有研究探讨逆境是否具有时间依赖性的影响，根据年龄在exposure.METHODS：使用两阶段结构化的生命历程建模方法，我们测试的假设，有敏感时期，逆境诱导更大的DNAm的变化。我们测试了这一假设的两个替代方案：积累假说，其中逆境的影响随着暴露的场合，无论时间的数量增加;和近因模型，其中逆境的影响更强的更近的事件。数据来自于整合表观基因组学研究的可扩展资源，一个来自Avon父母和孩子纵向研究的母子配对子样本（n = 691-774）。结果：经过协变量调整和多重检验校正，我们确定了38个CpG位点，这些位点在7岁时暴露于逆境后发生了差异甲基化。大多数位点（n = 35）预测的逆境，即曝光前3岁的时间。无论是积累还是最近的逆境解释相当大的变异DNAm。一个标准的表观全基因组关联研究的终身曝光（与没有曝光）未能检测到这些associations.CONCLUSIONS：逆境的发展时间解释更多的变异DNAm比积累或新近的曝光。非常早期的童年似乎是一个敏感的时期，当暴露于逆境预测差异DNAm模式。将个人分为早期生活逆境暴露者和未暴露者可能会淡化观察到的影响。
BACKGROUND: Exposure to early-life adversity is known to predict DNA methylation (DNAm) patterns that may be related to psychiatric risk. However, few studies have investigated whether adversity has time-dependent effects based on the age at exposure.METHODS: Using a two-stage structured life course modeling approach, we tested the hypothesis that there are sensitive periods when adversity induces greater DNAm changes. We tested this hypothesis in relation to two alternatives: an accumulation hypothesis, in which the effect of adversity increases with the number of occasions exposed, regardless of timing; and a recency model, in which the effect of adversity is stronger for more proximal events. Data came from the Accessible Resource for Integrated Epigenomic Studies, a subsample of mother-child pairs from the Avon Longitudinal Study of Parents and Children (n = 691-774).RESULTS: After covariate adjustment and multiple testing correction, we identified 38 CpG sites that were differentially methylated at 7 years of age following exposure to adversity. Most loci (n = 35) were predicted by the timing of adversity, namely exposures before 3 years of age. Neither the accumulation nor recency of the adversity explained considerable variability in DNAm. A standard epigenome-wide association study of lifetime exposure (vs. no exposure) failed to detect these associations.CONCLUSIONS: The developmental timing of adversity explains more variability in DNAm than the accumulation or recency of exposure. Very early childhood appears to be a sensitive period when exposure to adversity predicts differential DNAm patterns. Classification of individuals as exposed versus unexposed to early-life adversity may dilute observed effects.