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Homo sapiens

ABSTRACT: Gene expression associated with PTSD in World Trade Center responders: An RNA sequencing study

PROVIDER: PRJNA381549 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5412540.fastq.gz	Fastqsanger.gz
	SRR5412550.fastq.gz	Fastqsanger.gz
	SRR5412560.fastq.gz	Fastqsanger.gz
	SRR5412570.fastq.gz	Fastqsanger.gz
	SRR5412580.fastq.gz	Fastqsanger.gz

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Mapping the transcriptomics landscape of post-traumatic stress disorder symptom dimensions in World Trade Center responders

Project description:Gene expression has provided promising insights into the pathophysiology of posttraumatic stress disorder (PTSD), but specific regulatory transcriptomic mechanisms remain unknown. The current study addressed this limitation by analyzing transcriptome-wide RNA-Seq of whole blood samples from N=226 World Trade Center responders. The investigation focused on differential expression (DE) at gene, isoform, and alternative splicing (AS) levels associated with Posttraumatic Stress Disorder symptoms: total burden and its re-experiencing, avoidance, numbing, and hyperarousal subdimensions; and is the first study to characterize the AS landscape in PTSD. These dimensions were associated with 76, 1, 48, 15, and 49 genes, respectively (FDR<0.05). Similarly, they were associated with 103, 11, 0, 43, and 32 AS events. Avoidance differed the most from other dimensions with regard to DE genes, isoforms and AS correlates. Gene set enrichment analysis (GSEA) identified pathways involved in inflammatory and metabolic processes, which may have implications for the treatment of PTSD. Overall, findings shed a novel light on the wide range of transcriptomic alterations associated with PTSD at gene and AS levels. The DE analysis associated with PTSD subdimensions highlights the importance of studying PTSD symptom heterogeneity.

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Cell type specific gene expression patterns associated with posttraumatic stress disorder in World Trade Center responders

Project description:Posttraumatic stress disorder (PTSD) has been linked to immunologic dysregulation. Gene expression profiling has emerged as a promising tool for understanding the pathophysiology of PTSD. However, to date, all but one gene expression study was based on whole blood or unsorted peripheral blood mononuclear cell (PBMC), a complex tissue consisting of several populations of cells. The objective of this study was to utilize RNA sequencing to simultaneously profile the gene-expression of four immune cell subpopulations in World Trade Center responders. Pathway analyses identified gene sets related to immune response and inflammation as being among the differentially expressed genes in PTSD, including mast cell activation and regulation in CD4T, interferon-beta production in CD8T, and neutrophil related gene sets in monocytes. These findings are suggestive that immune cell dysregulation involves gene expression in various cell populations.

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Project description:Cell type specific gene expression patterns associated with posttraumatic stress disorder in World Trade Center responders

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Gene expression associated with PTSD in World Trade Center responders: An RNA sequencing study

Project description:The gene expression approach has provided promising insights into the pathophysiology of PTSD. However, few studies used hypothesis-free transcriptome-wide expression approach. Transcriptome-wide expression study using RNA sequencing (RNA-Seq) of whole blood was conducted in 324 World Trade Center responders (201 with never, 81 current and 42 past PTSD). The current and never PTSD samples were randomly split to form both discovery (N=195) and replication (N=87) cohorts. Differentially expressed genes identified in RNA-Seq were used in pathway analysis and to create a polygenic expression score. There were 448 differentially expressed genes in the discovery cohort, of which 99 remained significant in the replication cohort, and 5 (FKBP5, NDUFA1, CCDC85B, SNORD54, SNORD46) showed >1.2-fold difference in expression consistently between the discovery and replication cohorts. Several enriched biological pathways were found, including glucocorticoid receptor signaling and immunity-related pathways, but were not significant following FDR correction. The gene expression score achieved sensitivity of 0.917 and specificity of 0.508 for identifying PTSD cases in the replication cohort. It was similar in current and past PTSD, with both groups scoring higher than trauma-exposed controls. We confirmed the role of FKBP5 in PTSD and identified four additional differentially expressed genes that may constitute biomarkers for this condition. Together with the pathway analysis results, these findings point to HPA-axis and immune dysregulation as key biological processes underpinning PTSD. A novel polygenic expression aggregate that differentiates PTSD patients from trauma-exposed controls might be a useful screening tool for research and clinical practice, if replicated in other populations.

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Project description:High burden of Clonal Hematopoiesis in First Responders Exposed to the World Trade Center Disaster

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High burden of Clonal Hematopoiesis in First Responders Exposed to the World Trade Center Disaster

Project description:High burden of Clonal Hematopoiesis in First Responders Exposed to the World Trade Center Disaster

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