RNA-seq analysis of gene expression profiles in posttraumatic stress disorder, Parkinson\u2019s disease and schizophrenia identifies roles for common and distinct biological pathways

Sian M J Hemmings,Jonathan Carr,Nathaniel W Mcgregor,Soraya Bardien,Jacqueline S Womersely,Patricia Swart,Ellen S Ovenden,Soraya Seedat,Leigh L Van Den Heuvel,Robin Emsley,Gerard Tromp,Shameemah Abrahams,Stuart Meier

doi:10.1007/s44192-022-00009-y

Abstract

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.

Highlights

Psychiatric disorders, such as posttraumatic stress disorder (PTSD) and schizophrenia, and neurodegenerative disorders, such as Parkinson’s disease (PD), pose an immense burden to society [1, 2]
We identified multiple common KEGG pathway signatures across PTSD Module 2 and PD Module 3, including the KEGG “Ribosome”, “Oxidative phosphorylation”, “Parkinson’s Disease”, “Huntington’s Disease” and “Alzheimer’s Disease” pathways
Translational homeostasis can be disturbed by alterations in translation initiation rates or Ribosomal proteins (RPs) themselves, due to factors such as mutations or a decreased or increased number of normal ribosomes

Summary

Objectives

Due to converging lines of genetic, molecular, neurobiological and phenotypic evidence supporting shared pathophysiology underlying PTSD, PD and schizophrenia, we aimed to identify unique as well as shared pathways underlying these three disorders

Methods

Results

Conclusion