DNA methylation has been proposed as an epigenetic mechanism by which early-life experiences become “embedded” in the genome and alter transcriptional processes to compromise health. The authors sought to investigate whether early-life victimization stress is associated with genome-wide DNA methylation.

The authors tested the hypothesis that victimization is associated with DNA methylation in the Environmental Risk (E-Risk) Longitudinal Study, a nationally representative 1994–1995 birth cohort of 2,232 twins born in England and Wales and assessed at ages 5, 7, 10, 12, and 18 years. Multiple forms of victimization were ascertained in childhood and adolescence (including physical, sexual, and emotional abuse; neglect; exposure to intimate-partner violence; bullying; cyber-victimization; and crime).

Epigenome-wide analyses of polyvictimization across childhood and adolescence revealed few significant associations with DNA methylation in peripheral blood at age 18, but these analyses were confounded by tobacco smoking and/or did not survive co-twin control tests. Secondary analyses of specific forms of victimization revealed sparse associations with DNA methylation that did not replicate across different operationalizations of the same putative victimization experience. Hypothesis-driven analyses of six candidate genes in the stress response (NR3C1, FKBP5, BDNF, AVP, CRHR1, SLC6A4) did not reveal predicted associations with DNA methylation in probes annotated to these genes.

Findings from this epidemiological analysis of the epigenetic effects of early-life stress do not support the hypothesis of robust changes in DNA methylation in victimized young people. We need to come to terms with the possibility that epigenetic epidemiology is not yet well matched to experimental, nonhuman models in uncovering the biological embedding of stress.

DNA甲基化被认为是一种表观遗传机制，通过这种机制，早期生活经历“嵌入”基因组并改变转录过程以损害健康。作者试图调查早期受害压力是否与全基因组 DNA 甲基化有关。

作者在环境风险 (E-Risk) 纵向研究中检验了受害与 DNA 甲基化相关的假设，该研究是一项具有全国代表性的 1994-1995 年出生队列，包含 2,232 对在英格兰和威尔士出生并在 5、7、10 岁时进行评估的双胞胎， 12 岁和 18 岁。在儿童和青春期确定了多种形式的受害（包括身体、性和情感虐待；忽视；暴露于亲密伴侣暴力；欺凌；网络受害；和犯罪）。

对儿童和青春期多受害的表观基因组分析显示，18 岁时外周血 DNA 甲基化与 DNA 甲基化几乎没有显着关联，但这些分析被吸烟和/或在双胞胎对照测试中无法生存。对特定受害形式的二次分析揭示了与 DNA 甲基化的稀疏关联，这些关联并未在同一假定受害经历的不同操作中复制。对应激反应中六个候选基因（ NR3C1、FKBP5、BDNF、AVP、CRHR1、SLC6A4）的假设驱动分析未揭示与这些基因注释的探针中 DNA 甲基化的预测关联。

这项对早期生活压力的表观遗传影响的流行病学分析结果不支持受害年轻人 DNA 甲基化发生强烈变化的假设。我们需要接受表观遗传流行病学在揭示压力的生物嵌入方面尚未与实验性非人类模型很好地匹配的可能性。