Ohi Kazutaka, Fujikane Daisuke, Takai Kentaro, Kuramitsu Ayumi, Muto Yukimasa, Sugiyama Shunsuke, Shioiri Toshiki
Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan.
JMA J. 2025 Apr 28;8(2):363-370. doi: 10.31662/jmaj.2024-0329. Epub 2025 Feb 28.
DNA methylation is an epigenetic modification implicated in psychiatric disorders influenced by both genetic and environmental factors. Methylation risk scores (MRSs) have emerged as a tool for quantifying accumulated epigenetic modifications and assessing the predisposed risk for certain common disorders. This narrative review introduces the MRS application in psychiatric disorders, including schizophrenia (SCZ), bipolar disorder (BD), social anxiety disorder (SAD), and panic disorder (PD), while also discussing the current limitations and ethical considerations in psychiatric research. MRSs are calculated from epigenome-wide association studies (EWASs) for psychiatric disorders in various tissues from blood and brain and reflect methylation patterns associated with the psychiatric disorder risk. MRSs provide a perspective of how the cumulative methylation patterns at specific CpG sites may contribute to the onset of psychiatric disorders. In SCZ and BD, MRSs derived from both blood and brain tissues have shown distinct methylation profiles that differentiate these disorders, particularly in patients with a high genetic SCZ risk. MRSs are also used to assess the impact of environmental factors, such as early-life adversity and chronic stress, on psychiatric outcomes. In SAD and PD, where epigenetic studies are relatively limited, MRSs revealed both shared and distinct epigenetic features between anxiety disorders, with specific methylation changes associated with social avoidance in SAD patients. MRSs can serve as biomarkers, providing a valuable understanding of both genetic predispositions and environmental influences on gene regulation. However, the lack of large-scale EWAS datasets and standardized summary statistics remains as a limitation. To address this issue, this review provides a list of publicly available raw intensity data (IDAT) files from psychiatric epigenetic studies that can help facilitate future research by providing the raw data necessary for conducting independent EWASs and MRS calculations. As the field advances, careful consideration must be given to the ethical implications of MRS applications, particularly in clinical intervention and prevention. While MRSs hold promise for future personalized medicine applications, informing treatment decisions based on an individual's methylation profile, caution is warranted regarding their predictive utility and effect size limitations. This review emphasizes the importance of MRSs in advancing psychiatric research, bridging the gap between genetic risk and environmental factors.
DNA甲基化是一种表观遗传修饰，与受遗传和环境因素影响的精神疾病有关。甲基化风险评分（MRS）已成为一种量化累积表观遗传修饰和评估某些常见疾病易患风险的工具。这篇叙述性综述介绍了MRS在精神疾病中的应用，包括精神分裂症（SCZ）、双相情感障碍（BD）、社交焦虑障碍（SAD）和惊恐障碍（PD），同时也讨论了精神疾病研究中当前的局限性和伦理考量。MRS是根据来自血液和大脑等各种组织的精神疾病的全表观基因组关联研究（EWAS）计算得出的，反映了与精神疾病风险相关的甲基化模式。MRS提供了一个视角，即特定CpG位点的累积甲基化模式如何可能导致精神疾病的发作。在SCZ和BD中，来自血液和脑组织的MRS显示出不同的甲基化谱，这些谱可以区分这些疾病，特别是在具有高遗传SCZ风险的患者中。MRS还用于评估环境因素，如早期生活逆境和慢性应激，对精神疾病结局的影响。在表观遗传学研究相对有限的SAD和PD中，MRS揭示了焦虑症之间既有共同的也有不同的表观遗传特征，SAD患者中特定的甲基化变化与社交回避有关。MRS可以作为生物标志物，有助于深入了解遗传易感性和环境对基因调控的影响。然而缺乏大规模的EWAS数据集和标准化的汇总统计数据仍然是一个限制。为了解决这个问题，本综述提供了一份来自精神疾病表观遗传学研究的公开可用原始强度数据（IDAT）文件列表，通过提供进行独立EWAS和MRS计算所需的原始数据，有助于推动未来的研究。随着该领域的发展，必须仔细考虑MRS应用的伦理影响，特别是在临床干预和预防方面。虽然MRS有望用于未来的个性化医疗应用，根据个体的甲基化谱为治疗决策提供信息，但对于它们的预测效用和效应大小限制仍需谨慎对待。本综述强调了MRS在推进精神疾病研究、弥合遗传风险和环境因素之间差距方面的重要性。
