Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA.
Department of Medicine, Stony Brook University, Stony Brook, NY, USA.
Transl Psychiatry. 2021 May 24;11(1):310. doi: 10.1038/s41398-021-01431-6.
Gene expression has provided promising insights into the pathophysiology of post-traumatic stress disorder (PTSD); however, specific regulatory transcriptomic mechanisms remain unknown. The present study addressed this limitation by performing transcriptome-wide RNA-Seq of whole-blood samples from 226 World Trade Center responders. The investigation focused on differential expression (DE) at the gene, isoform, and for the first time, alternative splicing (AS) levels associated with the symptoms of PTSD: total burden, re-experiencing, avoidance, numbing, and hyperarousal subdimensions. These symptoms were associated with 76, 1, 48, 15, and 49 DE genes, respectively (FDR < 0.05). Moreover, they were associated with 103, 11, 0, 43, and 32 AS events. Avoidance differed the most from other dimensions with respect to DE genes and AS events. Gene set enrichment analysis (GSEA) identified pathways involved in inflammatory and metabolic processes, which may have implications in the treatment of PTSD. Overall, the findings shed a novel light on the wide range of transcriptomic alterations associated with PTSD at the gene and AS levels. The results of DE analysis associated with PTSD subdimensions highlights the importance of studying PTSD symptom heterogeneity.
基因表达为创伤后应激障碍（PTSD）的病理生理学提供了有希望的见解；然而，特定的调节转录组机制仍不清楚。本研究通过对 226 名世界贸易中心反应者的全血样本进行全转录组 RNA-Seq，解决了这一局限性。该研究集中于与 PTSD 症状相关的基因、异构体和首次（选择性）剪接（AS）水平的差异表达（DE）：总负担、再体验、回避、麻木和过度警觉亚维度。这些症状分别与 76、1、48、15 和 49 个 DE 基因相关（FDR<0.05）。此外，它们还与 103、11、0、43 和 32 个 AS 事件相关。与其他维度相比，回避在 DE 基因和 AS 事件方面差异最大。基因集富集分析（GSEA）鉴定了涉及炎症和代谢过程的途径，这可能对 PTSD 的治疗有影响。总的来说，这些发现为 PTSD 相关的基因和 AS 水平的广泛转录组改变提供了新的视角。与 PTSD 亚维度相关的 DE 分析结果强调了研究 PTSD 症状异质性的重要性。
