Supplementary Material for: Cross-species convergence of brain transcriptomic and epigenomic findings in posttraumatic stress disorder: A systematic review

Introduction: Posttraumatic stress disorder (PTSD) is a complex multifactorial disorder influenced by the interaction of genetic and environmental factors. Analyses of epigenomic and transcriptomic modifications may help to dissect the biological factors underlying the gene-environment interplay in PTSD. To date, most human PTSD epigenetics studies have used peripheral tissue, and these findings have complex and poorly-understood relationships to brain alterations. Studies examining brain tissue may help characterize the brain-specific transcriptomic and epigenomic profiles of PTSD. In this review, we compiled and integrate brain-specific molecular findings of PTSD from humans and animals. Methods: A systematic literature search according to the PRISMA criteria was performed to identify transcriptomic and epigenomic studies of PTSD, focusing on brain tissue from human postmortem samples or animal-stress paradigms. Results: Gene- and pathway-level convergence analyses revealed PTSD-dysregulated genes and biological pathways across brain regions and species. A total of 243 genes converged across species, 17 of them significantly enriched for PTSD. Chemical-synaptic transmission and signaling by G-protein-coupled receptors (GPCRs) were consistently enriched in across -omics and species. Discussion: Our findings point out dysregulated genes highly replicated across PTSD studies in humans and animal models and suggest a potential role for the corticotropin-releasing hormone/orexin pathway in PTSD’s pathophysiology. Further, we highlight current knowledge gaps and limitations and recommend future directions to address them.

引言：创伤后应激障碍（Posttraumatic stress disorder, PTSD）是一类受遗传与环境因素交互作用影响的复杂多因素疾患。表观基因组与转录组修饰分析，或可助力解析PTSD中基因-环境互作的生物学基础。迄今为止，多数人类PTSD表观遗传学研究均采用外周组织，且此类发现与脑部改变之间的关联复杂且尚未明确。针对脑组织的研究则有助于阐明PTSD的脑特异性转录组与表观基因组特征。本综述整合了源自人类与动物模型的PTSD脑特异性分子研究成果。

方法：本研究遵循系统评价与荟萃分析优先报告条目（PRISMA）标准开展系统性文献检索，旨在筛选PTSD的转录组与表观基因组研究，重点纳入人类死后脑组织样本或动物应激模型的脑组织相关研究。

结果：基因与通路水平的整合分析揭示了跨脑区与跨物种的PTSD失调基因及生物学通路。共计243个基因在跨物种分析中呈现一致失调，其中17个基因在PTSD相关研究中显著富集。化学突触传递以及G蛋白偶联受体（G-protein-coupled receptors, GPCRs）介导的信号通路，在多组学与跨物种分析中均持续呈现富集特征。

讨论：本研究发现了在人类与动物模型PTSD研究中高度重复的失调基因，并提示促肾上腺皮质激素释放激素/食欲素通路可能在PTSD的病理生理过程中发挥潜在作用。此外，本研究梳理了当前的研究空白与局限性，并提出了相应的未来研究方向。