Hemmings Sian M J, Swart Patricia, Womersely Jacqueline S, Ovenden Ellen S, van den Heuvel Leigh L, McGregor Nathaniel W, Meier Stuart, Bardien Soraya, Abrahams Shameemah, Tromp Gerard, Emsley Robin, Carr Jonathan, Seedat Soraya
Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa.
South African Medical Research Council/Stellenbosch University Genomics of Brain Disorders Research Unit, Stellenbosch University, Cape Town, South Africa.
Discov Ment Health. 2022 Mar 3;2(1):6. doi: 10.1007/s44192-022-00009-y.
Evidence suggests that shared pathophysiological mechanisms in neuropsychiatric disorders (NPDs) may contribute to risk and resilience. We used single-gene and network-level transcriptomic approaches to investigate shared and disorder-specific processes underlying posttraumatic stress disorder (PTSD), Parkinson's disease (PD) and schizophrenia in a South African sample. RNA-seq was performed on blood obtained from cases and controls from each cohort. Gene expression and weighted gene correlation network analyses (WGCNA) were performed using DESeq2 and CEMiTool, respectively. Significant differences in gene expression were limited to the PTSD cohort. However, WGCNA implicated, amongst others, ribosomal expression, inflammation and ubiquitination as key players in the NPDs under investigation. Differential expression in ribosomal-related pathways was observed in the PTSD and PD cohorts, and focal adhesion and extracellular matrix pathways were implicated in PD and schizophrenia. We propose that, despite different phenotypic presentations, core transdiagnostic mechanisms may play important roles in the molecular aetiology of NPDs.
有证据表明,神经精神疾病(NPDs)中共同的病理生理机制可能导致患病风险和恢复力。我们采用单基因和网络水平的转录组学方法,在一个南非样本中研究创伤后应激障碍(PTSD)、帕金森病(PD)和精神分裂症潜在的共同及疾病特异性过程。对每个队列的病例和对照所采集的血液进行RNA测序。分别使用DESeq2和CEMiTool进行基因表达分析和加权基因共表达网络分析(WGCNA)。基因表达的显著差异仅限于PTSD队列。然而,WGCNA表明,在所研究的NPDs中,核糖体表达、炎症和泛素化等是关键因素。在PTSD和PD队列中观察到核糖体相关途径的差异表达,而粘着斑和细胞外基质途径与PD和精神分裂症有关。我们提出,尽管有不同的表型表现,但核心的跨诊断机制可能在NPDs的分子病因学中起重要作用。