Investigating epigenetic consequences of early-life adversity: some methodological considerations

Stressful and traumatic events occurring during early childhood have been consistently associated with the development of psychiatric disorders later in life. This relationship may be mediated in part by epigenetic mechanisms, such as DNA methylation, which are influenced by the early-life environment. Epigenetic patterns can have lifelong effects on gene expression and on the functioning of biological processes relevant to stress reactivity and psychopathology. Optimization of epigenetic research activity necessitates a discussion surrounding the methodologies used for DNA methylation analysis, selection of tissue sources, and timing of psychological and biological assessments. Recent studies related to early-life adversity and methylation, including both candidate gene and epigenome-wide association studies, have drawn from the variety of available techniques to generate interesting data in the field. Further discussion is warranted to address the limitations inherent to this field of research, along with future directions for epigenetic studies of adversity-related psychopathology. We identified issues regarding sample characteristics in epigenetic studies of early life adversity. We compared methods and technologies used for candidate gene analysis and whole epigenome studies. We discussed future perspectives, including combining multiple forms of large-scale data and newer technologies.

儿童早期经历的应激性与创伤性事件，始终与日后精神障碍的发生发展存在稳定关联。该关联的部分介导机制，可能为受早期生活环境影响的表观遗传调控机制（epigenetic mechanism），例如DNA甲基化（DNA methylation）。表观遗传模式可对基因表达，以及与应激反应、精神病理相关的生物学过程的功能产生终身影响。优化表观遗传学研究工作，需围绕DNA甲基化分析方法、组织来源选择，以及心理与生物学评估的时间节点展开系统性讨论。近年来与早期生活逆境（early-life adversity）及甲基化相关的研究，涵盖候选基因研究与全表观基因组关联研究（epigenome-wide association study），均依托各类现有技术手段获取了该领域极具价值的研究数据。有必要针对该研究领域固有的局限性，以及逆境相关精神病理的表观遗传学研究的未来方向展开进一步探讨。本研究梳理了早期生活逆境表观遗传学研究中样本特征相关的若干问题，对比了候选基因分析与全表观基因组研究所采用的方法与技术，并探讨了未来研究前景，包括整合多类大规模数据与新兴技术手段。