Department of Evolutionary Biology, Ecology and Environmental Sciences, Faculty of Biology, University of Barcelona, Spain; Center for Biomedical Research in Mental Health (CIBERSAM), Spain.
Center for Biomedical Research in Mental Health (CIBERSAM), Spain; Unipolar Affective Disorders Program, Department of Psychiatry and Clinical Psychology, Hospital Clínic of Barcelona, Spain.
Neurosci Biobehav Rev. 2020 May;112:345-352. doi: 10.1016/j.neubiorev.2020.02.017. Epub 2020 Feb 14.
Monozygotic (MZ) twin studies constitute a key resource for the dissection of environmental and biological risk factors for human complex disorders. Given that epigenetic differences accumulate throughout the lifespan, the assessment of MZ twin pairs discordant for depression offers a genetically informative design to explore DNA methylation while accounting for the typical confounders of the field, shared by co-twins of a pair. In this review, we systematically evaluate all twin studies published to date assessing DNA methylation in association with depressive phenotypes. However, difficulty to recruit large numbers of MZ twin pairs fails to provide enough sample size to develop genome-wide approaches. Alternatively, region and pathway analysis revealed an enrichment for nervous system related functions; likewise, evidence supports an accumulation of methylation variability in affected subjects when compared to their co-twins. Nevertheless, longitudinal studies incorporating known risk factors for depression such as childhood trauma are required for understanding the role that DNA methylation plays in the etiology of depression.
同卵（MZ）双胞胎研究是解析人类复杂疾病的环境和生物风险因素的重要资源。鉴于表观遗传差异会在整个生命周期中积累，评估在抑郁方面存在差异的 MZ 双胞胎对提供了一个具有遗传信息的设计，可在考虑到该领域典型混杂因素（一对双胞胎共同具有的因素）的同时，探索 DNA 甲基化。在这篇综述中，我们系统地评估了迄今为止所有评估与抑郁表型相关的 DNA 甲基化的双胞胎研究。然而，招募大量 MZ 双胞胎的困难导致无法提供足够的样本量来开发全基因组方法。相反，区域和途径分析显示与神经系统相关功能相关的富集；同样，有证据表明，与同卵双胞胎相比，受影响的受试者的甲基化变异积累更多。然而，需要进行包括童年创伤等已知抑郁风险因素的纵向研究，以了解 DNA 甲基化在抑郁发病机制中的作用。
