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

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

PROVIDER: PRJNA692257 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13440900_1.fastq.gz	Fastqsanger.gz
	SRR13440900_2.fastq.gz	Fastqsanger.gz
	SRR13441000_1.fastq.gz	Fastqsanger.gz
	SRR13441000_2.fastq.gz	Fastqsanger.gz
	SRR13440901_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

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.

2021-06-03 | GSE164877 | GEO

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.

2018-12-17 | GSE114407 | GEO

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.

2018-02-13 | GSE97356 | GEO

Initial whole genome sequencing of plasma cell neoplasms in First Responders exposed to the World Trade Center attack of September 11, 2001

Project description:Initial whole genome sequencing of plasma cell neoplasms in First Responders exposed to the World Trade Center attack of September 11, 2001

| EGAS00001004467 | EGA

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

2021-12-05 | PRJEB49193 | EVA

Metabolomics of World Trade Center Exposed New York City Firefighters

Project description:Particulate matter (PM) exposure and metabolic syndrome (MetSyn) coexist in both industrialized and developing nations. PM and MetSyn are strong risk factors for chronic obstructive pulmonary disease (COPD) and asthma. After the World Trade Center collapse in 9/11/2001, PM-exposed individuals from the Fire Department of New York City (FDNY) developed a progressively lung disease. This nested case-cohort study is composed of never smoking, WTC exposed firefighters with normal pre-9/11 lung function presenting for subspecialty pulmonary evaluation (SPE) before March 2008. Representative cohort controls with serum drawn within six months of 9/11 (n=100). FEV1 at subspecialty exam defined cases: susceptible World Trade Center Lung Injury (WTC-LI) cases (n=50) had FEV1< lower limit of normal (LLN) and resistant WTC-LI cases with FEV1 ≥107% predicted (n=50). This study will determine the metabolomics profile that differentiates firefighters with WTC-LI, firefighters resistant to WTC-LI, and similarly exposed cohort controls.

2019-02-22 | ST001171 | MetabolomicsWorkbench

Traumatic exposures, posttraumatic stress disorder, and cognitive functioning in World Trade Center responders.

Project description:IntroductionThis study examined whether World Trade Center (WTC)-related exposures and posttraumatic stress disorder (PTSD) were associated with cognitive function and whether WTC responders' cognition differed from normative data.MethodsA computer-assisted neuropsychological battery was administered to a prospective cohort study of 1193 WTC responders with no history of stroke or WTC-related head injuries. Data were linked to information collected prospectively since 2002. Sample averages were compared to published norms.ResultsApproximately 14.8% of sampled responders had cognitive dysfunction. WTC responders had worse cognitive function compared to normative data. PTSD symptom severity and working >5 weeks on-site was associated with lower cognition.DiscussionResults from this sample highlight the potential for WTC responders to be experiencing an increased burden of cognitive dysfunction and linked lowered cognitive functioning to physical exposures and to PTSD. Future research is warranted to understand the extent to which cognitive dysfunction is evident in neural dysfunction.

| S-EPMC5700827 | biostudies-literature

Metabolomics analysis of post-traumatic stress disorder symptoms in World Trade Center responders.

Project description:Metabolomics has yielded promising insights into the pathophysiology of post-traumatic stress disorder (PTSD). The current study expands understanding of the systems-level effects of metabolites by using global metabolomics and complex lipid profiling in plasma samples from 124 World Trade Center responders (56 PTSD, 68 control) on 1628 metabolites. Differential metabolomics analysis identified hexosylceramide HCER(26:1) associated with PTSD at FDR < 0.1. The multi-metabolite composite score achieved an AUC of 0.839 for PTSD versus unaffected control classification. Independent component analysis identified three metabolomic modules significantly associated with PTSD. These modules were significantly enriched in bile acid metabolism, fatty acid metabolism and pregnenolone steroids, which are involved in innate immunity, inflammatory process and neuronal excitability, respectively. Integrative analysis of metabolomics and our prior proteomics datasets on subsample of 96 responders identified seven proteomic modules significantly correlated with metabolic modules. Overall, our findings shed light on the molecular alterations and identify metabolomic-proteomic signatures associated with PTSD by using machine learning and network approaches to enhance understanding of the pathways implicated in PTSD. If present results are confirmed in follow-up studies, they may inform development of novel treatments.

| S-EPMC9050707 | biostudies-literature

Transcriptomic analysis of World Trade Center particulate Matter-induced pulmonary inflammation and drug treatments

Project description:Transcriptomic analysis of World Trade Center particulate Matter-induced pulmonary inflammation and drug treatments

| PRJNA899045 | ENA

Glial suppression and post-traumatic stress disorder: A cross-sectional study of 1,520 world trade center responders.

Project description:BackgroundChronically re-experiencing the memory of a traumatic event might cause a glial response. This study examined whether glial activation would be associated with PTSD in a study of responders present after the 9/11 World Trade Center attacks without comorbid cerebrovascular disease.MethodsPlasma was retrieved from 1,520 WTC responders and stored for a cross-sectional sample of responders of varying levels of exposure and PTSD. Plasma levels (pg/ml) of glial fibrillary acidic protein (GFAP) were assayed. Because stroke and other cerebrovascular diseases cause distributional shifts in GFAP levels, multivariable-adjusted finite mixture models analyzed GFAP distributions in responders with and without possible cerebrovascular disease.ResultsResponders were aged 56.3 years and primarily male; 11.07% (n = 154) had chronic PTSD. Older age was associated with increased GFAP, whereas higher body mass was associated with decreased GFAP. Multivariable-adjusted finite mixture models revealed that severe re-experiencing trauma from 9/11 was associated with lower GFAP (B = -0.558, p = 0.003).ConclusionThis study presents evidence of reduced plasma GFAP levels among WTC responders with PTSD. Results suggest re-experiencing traumatic events might cause glial suppression.

| S-EPMC10209702 | biostudies-literature

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