Marti Jett - Academia.edu (original) (raw)

Papers by Marti Jett

Research paper thumbnail of Comparison of Transcriptional Signatures of Three Staphylococcal Superantigenic Toxins in Human Melanocytes

Biomedicines, Jun 14, 2022

Research paper thumbnail of Distinct Profiles of Cell-Free MicroRNAs in Plasma of Veterans with Post-Traumatic Stress Disorder

Journal of Clinical Medicine, Jul 3, 2019

Research paper thumbnail of Staphylococcal enterotoxin B: immunolabeling and visualization of target cells

Journal of Histochemistry and Cytochemistry, Mar 1, 1991

Research paper thumbnail of Investigating gene expression profiles of whole blood and peripheral blood mononuclear cells using multiple collection and processing methods

Research paper thumbnail of “GrimAge,” an epigenetic predictor of mortality, is accelerated in Major Depressive Disorder

medRxiv (Cold Spring Harbor Laboratory), Dec 30, 2020

Research paper thumbnail of Transcriptomes of Wet Skin Biopsies Predict Outcomes after Ionizing Radiation Exposure with Potential Dosimetric Applications in a Mouse Model

Current Issues in Molecular Biology, Aug 18, 2022

Research paper thumbnail of Rare copy number variation in posttraumatic stress disorder

Molecular Psychiatry

Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24–71%) psychiatric illness. Copy numbe... more Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24–71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. Th...

Research paper thumbnail of Diallyl Sulfide Attenuation of Carcinogenesis in Mammary Epithelial Cells through the Inhibition of ROS Formation, and DNA Strand Breaks

Biomolecules, 2021

Garlic has long been used medicinally for many diseases, including cancer. One of the active garl... more Garlic has long been used medicinally for many diseases, including cancer. One of the active garlic components is diallyl sulfide (DAS), which prevents carcinogenesis and reduces the incidence rate of several cancers. In this study, non-cancerous MCF-10A cells were used as a model to investigate the effect of DAS on Benzo (a)pyrene (BaP)-induced cellular carcinogenesis. The cells were evaluated based on changes in proliferation, cell cycle arrest, the formation of peroxides, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, the generation of DNA strand breaks, and DNA Polymerase β (Pol β) expression. The results obtained indicate that when co-treated with BaP, DAS inhibited BaP-induced cell proliferation (p < 0.05) to levels similar to the negative control. BaP treatment results in a two-fold increase in the accumulation of cells in the G2/M-phase of the cell cycle, which is restored to baseline levels, similar to untreated cells and vehicle-treated cells, when pretreated with 6 μM and...

Research paper thumbnail of Transcriptomics of Wet Skin Biopsies Predict Early Radiation-Induced Hematological Damage in a Mouse Model

Genes, 2022

The lack of an easy and fast radiation-exposure testing method with a dosimetric ability complica... more The lack of an easy and fast radiation-exposure testing method with a dosimetric ability complicates triage and treatment in response to a nuclear detonation, radioactive material release, or clandestine exposure. The potential of transcriptomics in radiation diagnosis and prognosis were assessed here using wet skin (blood/skin) biopsies obtained at hour 2 and days 4, 7, 21, and 28 from a mouse radiation model. Analysis of significantly differentially transcribed genes (SDTG; p ≤ 0.05 and FC ≥ 2) during the first post-exposure week identified the glycoprotein 6 (GP-VI) signaling, the dendritic cell maturation, and the intrinsic prothrombin activation pathways as the top modulated pathways with stable inactivation after lethal exposures (20 Gy) and intermittent activation after sublethal (1, 3, 6 Gy) exposure time points (TPs). Interestingly, these pathways were inactivated in the late TPs after sublethal exposure in concordance with a delayed deleterious effect. Modulated transcript...

Research paper thumbnail of Acute and Delayed Effects of Stress Eliciting Post-Traumatic Stress-Like Disorder Differentially Alters Fecal Microbiota Composition in a Male Mouse Model

Frontiers in Cellular and Infection Microbiology, 2022

The association between the shift in fecal resident microbiome and social conflicts with long-ter... more The association between the shift in fecal resident microbiome and social conflicts with long-term consequences on psychological plasticity, such as the development of post-traumatic stress disorder (PTSD), is yet to be comprehended. We developed an aggressor-exposed (Agg-E) social stress (SS) mouse model to mimic warzone-like conflicts, where random life-threatening interactions took place between naïve intruder mice and aggressive resident mice. Gradually these Agg-E mice developed distinct characteristics simulating PTSD-like aspects, whereas the control mice not exposed to Agg-E SS demonstrated distinct phenotypes. To further investigate the role of Agg-E SS on the resident microbiome, 16S rRNA gene sequencing was assayed using fecal samples collected at pre-, during, and post-SS time points. A time agonist shift in the fecal microbial composition of Agg-E mice in contrast to its controls suggested a persistent impact of Agg-E SS on resident microbiota. At the taxonomic level, A...

Research paper thumbnail of Utilization of machine learning for identifying symptom severity military-related PTSD subtypes and their biological correlates

Translational Psychiatry, 2021

We sought to find clinical subtypes of posttraumatic stress disorder (PTSD) in veterans 6–10 year... more We sought to find clinical subtypes of posttraumatic stress disorder (PTSD) in veterans 6–10 years post-trauma exposure based on current symptom assessments and to examine whether blood biomarkers could differentiate them. Samples were males deployed to Iraq and Afghanistan studied by the PTSD Systems Biology Consortium: a discovery sample of 74 PTSD cases and 71 healthy controls (HC), and a validation sample of 26 PTSD cases and 36 HC. A machine learning method, random forests (RF), in conjunction with a clustering method, partitioning around medoids, were used to identify subtypes derived from 16 self-report and clinician assessment scales, including the clinician-administered PTSD scale for DSM-IV (CAPS). Two subtypes were identified, designated S1 and S2, differing on mean current CAPS total scores: S2 = 75.6 (sd 14.6) and S1 = 54.3 (sd 6.6). S2 had greater symptom severity scores than both S1 and HC on all scale items. The mean first principal component score derived from clini...

Research paper thumbnail of Longitudinal genome-wide methylation study of PTSD treatment using prolonged exposure and hydrocortisone

Translational Psychiatry, 2021

Epigenetic changes are currently invoked as explanations for both the chronicity and tenacity of ... more Epigenetic changes are currently invoked as explanations for both the chronicity and tenacity of post-traumatic stress disorder (PTSD), a heterogeneous condition showing varying, sometimes idiosyncratic responses to treatment. This study evaluated epigenetic markers in the context of a randomized clinical trial of PTSD patients undergoing prolonged-exposure psychotherapy with and without a hydrocortisone augmentation prior to each session. The purpose of the longitudinal epigenome-wide analyses was to identify predictors of recovery (from pretreatment data) or markers associated with symptom change (based on differences between pre- and post-therapy epigenetic changes). The results of these analyses identified the CREB–BDNF signaling pathway, previously linked to startle reaction and fear learning and memory processes, as a convergent marker predicting both symptom change and severity. Several previous-reported resilience markers were also identified (FKBP5, NR3C1, SDK1, and MAD1L1)...

Research paper thumbnail of Early Transcriptomic Response to Burn Injury: Severe Burns Are Associated With Immune Pathway Shutdown

Journal of Burn Care & Research, 2021

Burn injury induces a systemic hyperinflammatory response with detrimental side effects. Studies ... more Burn injury induces a systemic hyperinflammatory response with detrimental side effects. Studies have described the biochemical changes induced by severe burns, but the transcriptome response is not well characterized. The goal of this work is to characterize the blood transcriptome after burn injury. Burn patients presenting to a regional center between 2012 and 2017 were prospectively enrolled. Blood was collected on admission and at predetermined time points (hours 2, 4, 8, 12, and 24). RNA was isolated and transcript levels were measured with a gene expression microarray. To identify differentially regulated genes (false-discovery rate ≤0.1) by burn injury severity, patients were grouped by TBSA above or below 20% and statistically enriched pathways were identified. Sixty-eight patients were analyzed, most patients were male with a median age of 41 (interquartile range, 30.5–58.5) years, and TBSA of 20% (11%–34%). Thirty-five patients had % TBSA injury ≥20%, and this group exper...

Research paper thumbnail of Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Biological Psychiatry, 2021

Research paper thumbnail of Epigenetic biotypes of post-traumatic stress disorder in war-zone exposed veteran and active duty males

Molecular Psychiatry, 2020

Post-traumatic stress disorder (PTSD) is a heterogeneous condition evidenced by the absence of ob... more Post-traumatic stress disorder (PTSD) is a heterogeneous condition evidenced by the absence of objective physiological measurements applicable to all who meet the criteria for the disorder as well as divergent responses to treatments. This study capitalized on biological diversity observed within the PTSD group observed following epigenome-wide analysis of a well-characterized Discovery cohort (N = 166) consisting of 83 male combat exposed veterans with PTSD, and 83 combat veterans without PTSD in order to identify patterns that might distinguish subtypes. Computational analysis of DNA methylation (DNAm) profiles identified two PTSD biotypes within the PTSD+ group, G1 and G2, associated with 34 clinical features that are associated with PTSD and PTSD comorbidities. The G2 biotype was associated with an increased PTSD risk and had higher polygenic risk scores and a greater methylation compared to the G1 biotype and healthy controls. The findings were validated at a 3-year follow-up (...

Research paper thumbnail of Evaluating the impact of trauma and PTSD on epigenetic prediction of lifespan and neural integrity

Neuropsychopharmacology, 2020

Research paper thumbnail of Poisoning with Soman, an Organophosphorus Nerve Agent, Alters Fecal Bacterial Biota and Urine Metabolites: a Case for Novel Signatures for Asymptomatic Nerve Agent Exposure

Applied and Environmental Microbiology, 2018

The paucity of assays to determine physiologically relevant OP exposure presents an opportunity t... more The paucity of assays to determine physiologically relevant OP exposure presents an opportunity to explore the use of fecal bacteria as sentinels in combination with urine to assess changes in the exposed host. Recent advances in sequencing technologies and computational approaches have enabled researchers to survey large community-level changes of gut bacterial biota and metabolomic changes in various biospecimens. Here, we profiled changes in fecal bacterial biota and urine metabolome following a chemical warfare nerve agent exposure. The significance of this work is a proof of concept that the fecal bacterial biota and urine metabolites are two separate biospecimens rich in surrogate indicators suitable for monitoring OP exposure. The larger value of such an approach is that assays developed on the basis of these observations can be deployed in any setting with moderate clinical chemistry and microbiology capability. This can enable estimation of the affected radius as well as sc...

Research paper thumbnail of Molecular genetic overlap between posttraumatic stress disorder and sleep phenotypes

Sleep, 2019

Study ObjectivesSleep problems are common, serving as both a predictor and symptom of posttraumat... more Study ObjectivesSleep problems are common, serving as both a predictor and symptom of posttraumatic stress disorder (PTSD), with these bidirectional relationships well established in the literature. While both sleep phenotypes and PTSD are moderately heritable, there has been a paucity of investigation into potential genetic overlap between sleep and PTSD. Here, we estimate genetic correlations between multiple sleep phenotypes (including insomnia symptoms, sleep duration, daytime sleepiness, and chronotype) and PTSD, using results from the largest genome-wide association study (GWAS) to date of PTSD, as well as publicly available GWAS results for sleep phenotypes within UK Biobank data (23 variations, encompassing four main phenotypes).MethodsGenetic correlations were estimated utilizing linkage disequilibrium score regression (LDSC), an approach that uses GWAS summary statistics to compute genetic correlations across traits, and Mendelian randomization (MR) analyses were conducted...

Research paper thumbnail of Metabolomic analysis of male combat veterans with post traumatic stress disorder

Research paper thumbnail of Multi-omic biomarker identification and validation for diagnosing warzone-related post-traumatic stress disorder

Molecular Psychiatry, 2019

Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnos... more Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnosis can be problematic due to biases in self-disclosure of symptoms, stigma within military populations, and limitations identifying those at risk. Prior studies suggest that PTSD may be a systemic illness, affecting not just the brain, but the entire body. Therefore, disease signals likely span multiple biological domains, including genes, proteins, cells, tissues, and organism-level physiological changes. Identification of these signals could aid in diagnostics, treatment decision-making, and risk evaluation. In the search for PTSD diagnostic biomarkers, we ascertained over one million molecular, cellular, physiological, and clinical features from three cohorts of male veterans. In a discovery cohort of 83 warzone-related PTSD cases and 82 warzone-exposed controls, we identified a set of 343 candidate biomarkers. These candidate biomarkers were selected from an integrated approach using...

Research paper thumbnail of Comparison of Transcriptional Signatures of Three Staphylococcal Superantigenic Toxins in Human Melanocytes

Biomedicines, Jun 14, 2022

Research paper thumbnail of Distinct Profiles of Cell-Free MicroRNAs in Plasma of Veterans with Post-Traumatic Stress Disorder

Journal of Clinical Medicine, Jul 3, 2019

Research paper thumbnail of Staphylococcal enterotoxin B: immunolabeling and visualization of target cells

Journal of Histochemistry and Cytochemistry, Mar 1, 1991

Research paper thumbnail of Investigating gene expression profiles of whole blood and peripheral blood mononuclear cells using multiple collection and processing methods

Research paper thumbnail of “GrimAge,” an epigenetic predictor of mortality, is accelerated in Major Depressive Disorder

medRxiv (Cold Spring Harbor Laboratory), Dec 30, 2020

Research paper thumbnail of Transcriptomes of Wet Skin Biopsies Predict Outcomes after Ionizing Radiation Exposure with Potential Dosimetric Applications in a Mouse Model

Current Issues in Molecular Biology, Aug 18, 2022

Research paper thumbnail of Rare copy number variation in posttraumatic stress disorder

Molecular Psychiatry

Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24–71%) psychiatric illness. Copy numbe... more Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24–71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. Th...

Research paper thumbnail of Diallyl Sulfide Attenuation of Carcinogenesis in Mammary Epithelial Cells through the Inhibition of ROS Formation, and DNA Strand Breaks

Biomolecules, 2021

Garlic has long been used medicinally for many diseases, including cancer. One of the active garl... more Garlic has long been used medicinally for many diseases, including cancer. One of the active garlic components is diallyl sulfide (DAS), which prevents carcinogenesis and reduces the incidence rate of several cancers. In this study, non-cancerous MCF-10A cells were used as a model to investigate the effect of DAS on Benzo (a)pyrene (BaP)-induced cellular carcinogenesis. The cells were evaluated based on changes in proliferation, cell cycle arrest, the formation of peroxides, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, the generation of DNA strand breaks, and DNA Polymerase β (Pol β) expression. The results obtained indicate that when co-treated with BaP, DAS inhibited BaP-induced cell proliferation (p < 0.05) to levels similar to the negative control. BaP treatment results in a two-fold increase in the accumulation of cells in the G2/M-phase of the cell cycle, which is restored to baseline levels, similar to untreated cells and vehicle-treated cells, when pretreated with 6 μM and...

Research paper thumbnail of Transcriptomics of Wet Skin Biopsies Predict Early Radiation-Induced Hematological Damage in a Mouse Model

Genes, 2022

The lack of an easy and fast radiation-exposure testing method with a dosimetric ability complica... more The lack of an easy and fast radiation-exposure testing method with a dosimetric ability complicates triage and treatment in response to a nuclear detonation, radioactive material release, or clandestine exposure. The potential of transcriptomics in radiation diagnosis and prognosis were assessed here using wet skin (blood/skin) biopsies obtained at hour 2 and days 4, 7, 21, and 28 from a mouse radiation model. Analysis of significantly differentially transcribed genes (SDTG; p ≤ 0.05 and FC ≥ 2) during the first post-exposure week identified the glycoprotein 6 (GP-VI) signaling, the dendritic cell maturation, and the intrinsic prothrombin activation pathways as the top modulated pathways with stable inactivation after lethal exposures (20 Gy) and intermittent activation after sublethal (1, 3, 6 Gy) exposure time points (TPs). Interestingly, these pathways were inactivated in the late TPs after sublethal exposure in concordance with a delayed deleterious effect. Modulated transcript...

Research paper thumbnail of Acute and Delayed Effects of Stress Eliciting Post-Traumatic Stress-Like Disorder Differentially Alters Fecal Microbiota Composition in a Male Mouse Model

Frontiers in Cellular and Infection Microbiology, 2022

The association between the shift in fecal resident microbiome and social conflicts with long-ter... more The association between the shift in fecal resident microbiome and social conflicts with long-term consequences on psychological plasticity, such as the development of post-traumatic stress disorder (PTSD), is yet to be comprehended. We developed an aggressor-exposed (Agg-E) social stress (SS) mouse model to mimic warzone-like conflicts, where random life-threatening interactions took place between naïve intruder mice and aggressive resident mice. Gradually these Agg-E mice developed distinct characteristics simulating PTSD-like aspects, whereas the control mice not exposed to Agg-E SS demonstrated distinct phenotypes. To further investigate the role of Agg-E SS on the resident microbiome, 16S rRNA gene sequencing was assayed using fecal samples collected at pre-, during, and post-SS time points. A time agonist shift in the fecal microbial composition of Agg-E mice in contrast to its controls suggested a persistent impact of Agg-E SS on resident microbiota. At the taxonomic level, A...

Research paper thumbnail of Utilization of machine learning for identifying symptom severity military-related PTSD subtypes and their biological correlates

Translational Psychiatry, 2021

We sought to find clinical subtypes of posttraumatic stress disorder (PTSD) in veterans 6–10 year... more We sought to find clinical subtypes of posttraumatic stress disorder (PTSD) in veterans 6–10 years post-trauma exposure based on current symptom assessments and to examine whether blood biomarkers could differentiate them. Samples were males deployed to Iraq and Afghanistan studied by the PTSD Systems Biology Consortium: a discovery sample of 74 PTSD cases and 71 healthy controls (HC), and a validation sample of 26 PTSD cases and 36 HC. A machine learning method, random forests (RF), in conjunction with a clustering method, partitioning around medoids, were used to identify subtypes derived from 16 self-report and clinician assessment scales, including the clinician-administered PTSD scale for DSM-IV (CAPS). Two subtypes were identified, designated S1 and S2, differing on mean current CAPS total scores: S2 = 75.6 (sd 14.6) and S1 = 54.3 (sd 6.6). S2 had greater symptom severity scores than both S1 and HC on all scale items. The mean first principal component score derived from clini...

Research paper thumbnail of Longitudinal genome-wide methylation study of PTSD treatment using prolonged exposure and hydrocortisone

Translational Psychiatry, 2021

Epigenetic changes are currently invoked as explanations for both the chronicity and tenacity of ... more Epigenetic changes are currently invoked as explanations for both the chronicity and tenacity of post-traumatic stress disorder (PTSD), a heterogeneous condition showing varying, sometimes idiosyncratic responses to treatment. This study evaluated epigenetic markers in the context of a randomized clinical trial of PTSD patients undergoing prolonged-exposure psychotherapy with and without a hydrocortisone augmentation prior to each session. The purpose of the longitudinal epigenome-wide analyses was to identify predictors of recovery (from pretreatment data) or markers associated with symptom change (based on differences between pre- and post-therapy epigenetic changes). The results of these analyses identified the CREB–BDNF signaling pathway, previously linked to startle reaction and fear learning and memory processes, as a convergent marker predicting both symptom change and severity. Several previous-reported resilience markers were also identified (FKBP5, NR3C1, SDK1, and MAD1L1)...

Research paper thumbnail of Early Transcriptomic Response to Burn Injury: Severe Burns Are Associated With Immune Pathway Shutdown

Journal of Burn Care & Research, 2021

Burn injury induces a systemic hyperinflammatory response with detrimental side effects. Studies ... more Burn injury induces a systemic hyperinflammatory response with detrimental side effects. Studies have described the biochemical changes induced by severe burns, but the transcriptome response is not well characterized. The goal of this work is to characterize the blood transcriptome after burn injury. Burn patients presenting to a regional center between 2012 and 2017 were prospectively enrolled. Blood was collected on admission and at predetermined time points (hours 2, 4, 8, 12, and 24). RNA was isolated and transcript levels were measured with a gene expression microarray. To identify differentially regulated genes (false-discovery rate ≤0.1) by burn injury severity, patients were grouped by TBSA above or below 20% and statistically enriched pathways were identified. Sixty-eight patients were analyzed, most patients were male with a median age of 41 (interquartile range, 30.5–58.5) years, and TBSA of 20% (11%–34%). Thirty-five patients had % TBSA injury ≥20%, and this group exper...

Research paper thumbnail of Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Biological Psychiatry, 2021

Research paper thumbnail of Epigenetic biotypes of post-traumatic stress disorder in war-zone exposed veteran and active duty males

Molecular Psychiatry, 2020

Post-traumatic stress disorder (PTSD) is a heterogeneous condition evidenced by the absence of ob... more Post-traumatic stress disorder (PTSD) is a heterogeneous condition evidenced by the absence of objective physiological measurements applicable to all who meet the criteria for the disorder as well as divergent responses to treatments. This study capitalized on biological diversity observed within the PTSD group observed following epigenome-wide analysis of a well-characterized Discovery cohort (N = 166) consisting of 83 male combat exposed veterans with PTSD, and 83 combat veterans without PTSD in order to identify patterns that might distinguish subtypes. Computational analysis of DNA methylation (DNAm) profiles identified two PTSD biotypes within the PTSD+ group, G1 and G2, associated with 34 clinical features that are associated with PTSD and PTSD comorbidities. The G2 biotype was associated with an increased PTSD risk and had higher polygenic risk scores and a greater methylation compared to the G1 biotype and healthy controls. The findings were validated at a 3-year follow-up (...

Research paper thumbnail of Evaluating the impact of trauma and PTSD on epigenetic prediction of lifespan and neural integrity

Neuropsychopharmacology, 2020

Research paper thumbnail of Poisoning with Soman, an Organophosphorus Nerve Agent, Alters Fecal Bacterial Biota and Urine Metabolites: a Case for Novel Signatures for Asymptomatic Nerve Agent Exposure

Applied and Environmental Microbiology, 2018

The paucity of assays to determine physiologically relevant OP exposure presents an opportunity t... more The paucity of assays to determine physiologically relevant OP exposure presents an opportunity to explore the use of fecal bacteria as sentinels in combination with urine to assess changes in the exposed host. Recent advances in sequencing technologies and computational approaches have enabled researchers to survey large community-level changes of gut bacterial biota and metabolomic changes in various biospecimens. Here, we profiled changes in fecal bacterial biota and urine metabolome following a chemical warfare nerve agent exposure. The significance of this work is a proof of concept that the fecal bacterial biota and urine metabolites are two separate biospecimens rich in surrogate indicators suitable for monitoring OP exposure. The larger value of such an approach is that assays developed on the basis of these observations can be deployed in any setting with moderate clinical chemistry and microbiology capability. This can enable estimation of the affected radius as well as sc...

Research paper thumbnail of Molecular genetic overlap between posttraumatic stress disorder and sleep phenotypes

Sleep, 2019

Study ObjectivesSleep problems are common, serving as both a predictor and symptom of posttraumat... more Study ObjectivesSleep problems are common, serving as both a predictor and symptom of posttraumatic stress disorder (PTSD), with these bidirectional relationships well established in the literature. While both sleep phenotypes and PTSD are moderately heritable, there has been a paucity of investigation into potential genetic overlap between sleep and PTSD. Here, we estimate genetic correlations between multiple sleep phenotypes (including insomnia symptoms, sleep duration, daytime sleepiness, and chronotype) and PTSD, using results from the largest genome-wide association study (GWAS) to date of PTSD, as well as publicly available GWAS results for sleep phenotypes within UK Biobank data (23 variations, encompassing four main phenotypes).MethodsGenetic correlations were estimated utilizing linkage disequilibrium score regression (LDSC), an approach that uses GWAS summary statistics to compute genetic correlations across traits, and Mendelian randomization (MR) analyses were conducted...

Research paper thumbnail of Metabolomic analysis of male combat veterans with post traumatic stress disorder

Research paper thumbnail of Multi-omic biomarker identification and validation for diagnosing warzone-related post-traumatic stress disorder

Molecular Psychiatry, 2019

Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnos... more Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnosis can be problematic due to biases in self-disclosure of symptoms, stigma within military populations, and limitations identifying those at risk. Prior studies suggest that PTSD may be a systemic illness, affecting not just the brain, but the entire body. Therefore, disease signals likely span multiple biological domains, including genes, proteins, cells, tissues, and organism-level physiological changes. Identification of these signals could aid in diagnostics, treatment decision-making, and risk evaluation. In the search for PTSD diagnostic biomarkers, we ascertained over one million molecular, cellular, physiological, and clinical features from three cohorts of male veterans. In a discovery cohort of 83 warzone-related PTSD cases and 82 warzone-exposed controls, we identified a set of 343 candidate biomarkers. These candidate biomarkers were selected from an integrated approach using...