DNA Methylation Patterns of Chronic Explosive Breaching in U.S. Military Warfighters
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PROVIDER: PRJNA649737 | ENA |
REPOSITORIES: ENA
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Project description:Epigenetic profiles in peripheral blood samples from 59 subjects (in two separate U.S. Military training sessions) were screened using Illumina Infinium MethylationEPIC BeadChips, session 2 (31 subjects) were also screened post-exposure to a controlled, low-level blast during a 3-day explosive breaching course. Participants had varying numbers of exposures to blast over their military careers (empirically defined as high ≥ 40, and conversely, low < 39 breaching exposures) at baseline. Daily self-reported physiological symptoms were recorded.
2020-08-24 | GSE155426 | GEO
Project description:Background: Injuries from exposure to explosions rose dramatically during the Iraq and Afghanistan wars, which motivated investigation of blast-related neurotrauma. We have undertaken human studies involving military "breachers" -exposed to controlled, low-level blast during a 3-days explosive breaching course. Methods: We screened epigenetic profiles in peripheral blood samples from 59 subjects (in two separate U.S. Military training sessions) using Infinium MethylationEPIC BeadChips. Participants had varying numbers of exposures to blast over their military careers (empirically defined as high ≥ 40, and conversely, low < 39 breaching exposures). Daily self-reported physiological symptoms were recorded. Tinnitus, memory problems, headaches, and sleep disturbances are most frequently reported. Results: We identified 14 significantly differentially methylated regions (DMRs) within genes associated with cumulative blast exposure in participants with high relative to low cumulative blast exposure. Notably, NTSR1 and SPON1 were significantly differentially methylated in high relative to low blast exposed groups, suggesting that sleep dysregulation may be altered in response to chronic cumulative blast exposure. In comparing lifetime blast exposure at baseline (prior to exposure in current training), and top associated symptoms, we identified significant DMRs associated with tinnitus, sleep difficulties, and headache. Notably, we identified KCNN3, SOD3, MUC4, GALR1, and WDR45B, which are implicated in auditory function, as differentially methylated associated with self-reported tinnitus. These findings suggest neurobiological mechanisms behind auditory injuries in our military warfighters and are particularly relevant given tinnitus is not only a primary disability among veterans, but has also been demonstrated in active duty medical records for populations exposed to blast in training. Additionally, we found that differentially methylated regions associated with the genes CCDC68 and COMT track with sleep difficulties, and those within FMOD and TNXB track with pain and headache. Conclusion: Sleep disturbances, as well as tinnitus and chronic pain, are widely reported in U.S. military service members and veterans. As we have previously demonstrated, DNA methylation encapsulates lifetime exposure to blast. The current data support previous findings and recapitulate transcriptional regulatory alterations in genes involved in sleep, auditory function, and pain. These data uncovered novel epigenetic and transcriptional regulatory mechanism underlying the etiological basis of these symptoms.
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Project description:Post-Traumatic Stress Disorder is a mental health condition that may develop after exposure to a traumatic event. The diagnosis of PTSD is based on clinical signs and symptoms; there is increasing evidence that biological markers aid in the diagnosis of PTSD. In a Dutch military cohort, we compared blood-based transcriptomic profiles of individuals susceptible and resilient to developing PTSD symptoms after combat-trauma exposure. Whole blood samples were collected from susceptible (n=20) and resilient (n=20) military personnel deployed to Afghanistan, 6 months after returning from military deployment.
2024-11-30 | E-MTAB-13185 | biostudies-arrayexpress
Project description:Identification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-associated DNA methylation patterns
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Project description:Many veterans live with military grade heavy metal fragments retained in soft tissue. Retained heavy metal fragments may negatively impact health in various organ systems and can manifest as gastrointestinal, neurocognitive, pulmonary and renal disturbances. As such, a better understanding of the long-term effects of retained metals and identification of biomarkers indicative of detrimental health outcomes would benefit clinical decision making. In this study, we analyzed serum microRNAs from rats with military-relevant pure metals implanted in the gastrocnemius muscle for 1, 3, 6, and 12 months in order to identify potential microRNA biomarkers that are indicative of exposure to one or more metals.
2023-05-01 | GSE168757 | GEO
Project description:U.S. Tijuana River Surface Water Samples Metagenome (2019-2020)
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Project description:We reveal differential reprogramming of the circadian transcriptome in the liver using acute versus chronic ethanol feeding. Specifically, rewiring of diurnal SREBP transcriptional pathway leads to distinct hepatic signatures in acetyl-CoA metabolism that are translated into the subcellular patterns of protein acetylation distinct to chronic exposure to ethanol. Therefore, distinct drinking patterns of alcohol result in differential circadian reprogramming that may contribute to ALD pathogenesis.
2019-11-30 | GSE132103 | GEO
Project description:Acinetobacter baumannii collected within the U.S. military healthcare system
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Project description:Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex condition that involves multiple organ systems and is characterized by an abrupt or delayed onset of persistent/relapsing symptomatology such as debilitating fatigue, immune dysfunction, neurological problems, and other symptoms not curable for at least 6 months. Disruption of DNA methylation patterns has been tied to various immune and neurological diseases; however, the status of this epigenetic mark in ME/CFS remains uncertain. This study aimed at identifying changes in the DNA methylation patterns that are causative of changes in the regulation of gene expression in ME/CSF patients. Such changes may be also used for diagnostic purposes and be indicative of potential therapeutic targets. Methods: Peripheral blood mononuclear cells (PBMCs) from 13 ME/CFS patients and 12 healthy controls (HC) were used to extract genomic DNA and measure global DNA methylation, and the methylation status at 850,000 CpG sites was assessed using Illumina MethylationEPIC microarrays. Results: Global DNA methylation levels of ME/CFS patients were similar to those of HC. However, microarray-based genome-wide technology allowed detection of 17,296 differentially methylated CpG sites in 6,368 genes across promoters, gene regulatory elements and within coding regions of genes. Analysis of DNA methylation in promoter regions found 307 differentially methylated promoters (DMP); genes associated with DMP participate in at least 15 different pathways mostly related to cell signaling with a strong immune component. Conclusions: This is the first study that has explored genome-wide epigenetic changes associated with ME/CFS using the new MethylationEPIC microarrays covering about 850,000 CpG sites. Our results are consistent with dysregulation of the immune system in ME/CFS and suggest a role of this epigenetic modification on the DNA pathobiology of ME/CFS.
2018-07-23 | GSE111183 | GEO