Bountress Kaitlin E, Vladimirov Vladimir, McMichael Gowon, Taylor Z Nathan, Hardiman Gary, Chung Dongjun, Adams Zachary W, Danielson Carla Kmett, Amstadter Ananda B
Virginia Institute for Psychiatry and Behavioral Genetics, Virginia Commonwealth University (VCU), Richmond, VA, United States.
Department of Psychiatry and Behavioral Sciences, College of Medicine Texas A&M University, Richmond, VA, United States.
Front Psychiatry. 2021 Apr 8;12:581093. doi: 10.3389/fpsyt.2021.581093. eCollection 2021.
The purpose of this study was to identify gene expression differences associated with post-traumatic stress disorder (PTSD) and trauma exposure (TE) in a three-group study design comprised of those with and without trauma exposure and PTSD. We conducted gene expression and gene network analyses in a sample ( = 45) composed of female subjects of European Ancestry (EA) with PTSD, TE without PTSD, and controls. We identified 283 genes differentially expressed between PTSD-TE groups. In an independent sample of Veterans ( = 78) a small minority of these genes were also differentially expressed. We identified 7 gene network modules significantly associated with PTSD and TE (Bonferroni corrected ≤ 0.05), which at a false discovery rate (FDR) of ≤ 0.2, were significantly enriched for biological pathways involved in focal adhesion, neuroactive ligand receptor interaction, and immune related processes among others. This study uses gene network analyses to identify significant gene modules associated with PTSD, TE, and controls. On an individual gene level, we identified a large number of differentially expressed genes between PTSD-TE groups, a minority of which were also differentially expressed in the independent sample. We also demonstrate a lack of network module preservation between PTSD and TE, suggesting that the molecular signature of PTSD and trauma are likely independent of each other. Our results provide a basis for the identification of likely disease pathways and biomarkers involved in the etiology of PTSD.
本研究的目的是在一项三组研究设计中,确定与创伤后应激障碍(PTSD)和创伤暴露(TE)相关的基因表达差异,该设计包括有或无创伤暴露及PTSD的个体。我们对一个由患有PTSD的欧洲裔(EA)女性受试者、有TE但无PTSD的女性受试者以及对照组组成的样本(n = 45)进行了基因表达和基因网络分析。我们确定了PTSD-TE组之间有283个基因差异表达。在一个独立的退伍军人样本(n = 78)中,这些基因中只有一小部分也存在差异表达。我们确定了7个与PTSD和TE显著相关的基因网络模块(Bonferroni校正P≤0.05),在错误发现率(FDR)≤0.2时,这些模块在粘着斑、神经活性配体受体相互作用以及免疫相关过程等生物学途径中显著富集。本研究使用基因网络分析来确定与PTSD、TE和对照组相关的重要基因模块。在个体基因水平上,我们确定了PTSD-TE组之间有大量差异表达基因,其中只有一小部分在独立样本中也存在差异表达。我们还证明了PTSD和TE之间缺乏网络模块的一致性,这表明PTSD和创伤的分子特征可能彼此独立。我们的结果为确定PTSD病因中可能涉及的疾病途径和生物标志物提供了依据。