Dataset Information

Epigenome-wide association study of posttraumatic stress disorder identifies novel loci in U.S. military veterans.

ABSTRACT: Posttraumatic stress disorder (PTSD) is a chronic and disabling psychiatric disorder prevalent in military veterans. Epigenetic mechanisms have been implicated in the etiology of PTSD, with DNA methylation being the most studied to identify novel molecular biomarkers associated with this disorder. We performed one of the largest single-sample epigenome-wide association studies (EWAS) of PTSD to date. Our sample included 1135 male European-American U.S. veterans who participated in the National Health and Resilience in Veterans Study (NHRVS). DNA was collected from saliva samples and the Illumina HumanMethylation EPIC BeadChip was used for the methylation analysis. PTSD was assessed using the PTSD Checklist. An EWAS was conducted using linear regression adjusted for age, cell-type proportions, first 10 principal components, and smoking status. After Bonferroni correction, we identified six genome-wide significant (GWS) CpG sites associated with past-month PTSD and three CpGs with lifetime PTSD (p_range = 10^-10-10^-8). These CpG sites map to genes involved in immune function, transcription regulation, axonal guidance, cell signaling, and protein binding. Among these, SENP7, which is involved in transcription regulation and has been linked to risk-taking behavior and alcohol consumption in genome-wide association studies, replicated in an independent veteran cohort and was downregulated in medial orbitofrontal cortex of PTSD postmortem brain tissue. These findings suggest potential epigenetic biomarkers of PTSD that may help inform the pathophysiology of this disorder in veterans and other trauma-affected populations.

SUBMITTER: Montalvo-Ortiz JL

PROVIDER: S-EPMC8854688 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Epigenome-wide association study of posttraumatic stress disorder identifies novel loci in U.S. military veterans.

Montalvo-Ortiz Janitza L JL Gelernter Joel J Cheng Zhongshan Z Girgenti Matthew J MJ Xu Ke K Zhang Xinyu X Gopalan Shyamalika S Zhou Hang H Duman Ronald S RS Southwick Steven M SM Krystal John H JH Pietrzak Robert H RH

Translational psychiatry 20220217 1

Posttraumatic stress disorder (PTSD) is a chronic and disabling psychiatric disorder prevalent in military veterans. Epigenetic mechanisms have been implicated in the etiology of PTSD, with DNA methylation being the most studied to identify novel molecular biomarkers associated with this disorder. We performed one of the largest single-sample epigenome-wide association studies (EWAS) of PTSD to date. Our sample included 1135 male European-American U.S. veterans who participated in the National H ...[more]

PMID: 35177594

Similar Datasets

Project description:BackgroundPrevious studies using candidate gene and genome-wide approaches have identified epigenetic changes in DNA methylation (DNAm) associated with posttraumatic stress disorder (PTSD).MethodsIn this study, we performed an EWAS of PTSD in a cohort of Veterans (n = 378 lifetime PTSD cases and 135 controls) from the Translational Research Center for TBI and Stress Disorders (TRACTS) cohort assessed using the Illumina EPIC Methylation BeadChip which assesses DNAm at more than 850,000 sites throughout the genome. Our model included covariates for ancestry, cell heterogeneity, sex, age, and a smoking score based on DNAm at 39 smoking-associated CpGs. We also examined in EPIC-based DNAm data generated from pre-frontal cortex (PFC) tissue from the National PTSD Brain Bank (n = 72).ResultsThe analysis of blood samples yielded one genome-wide significant association with PTSD at cg19534438 in the gene G0S2 (p = 1.19 × 10-7, padj = 0.048). This association was replicated in an independent PGC-PTSD-EWAS consortium meta-analysis of military cohorts (p = 0.0024). We also observed association with the smoking-related locus cg05575921 in AHRR despite inclusion of a methylation-based smoking score covariate (p = 9.16 × 10-6), which replicates a previously observed PGC-PTSD-EWAS association (Smith et al. 2019), and yields evidence consistent with a smoking-independent effect. The top 100 EWAS loci were then examined in the PFC data. One of the blood-based PTSD loci, cg04130728 in CHST11, which was in the top 10 loci in blood, but which was not genome-wide significant, was significantly associated with PTSD in brain tissue (in blood p = 1.19 × 10-5, padj = 0.60, in brain, p = 0.00032 with the same direction of effect). Gene set enrichment analysis of the top 500 EWAS loci yielded several significant overlapping GO terms involved in pathogen response, including "Response to lipopolysaccharide" (p = 6.97 × 10-6, padj = 0.042).ConclusionsThe cross replication observed in independent cohorts is evidence that DNA methylation in peripheral tissue can yield consistent and replicable PTSD associations, and our results also suggest that that some PTSD associations observed in peripheral tissue may mirror associations in the brain.

Project description:Recent work inspired by graph theory has begun to conceptualize mental disorders as networks of interacting symptoms. Posttraumatic stress disorder (PTSD) symptom networks have been investigated in clinical samples meeting full diagnostic criteria, including military veterans, natural disaster survivors, civilian survivors of war, and child sexual abuse survivors. Despite reliable associations across reported networks, more work is needed to compare central symptoms across trauma types. Additionally, individuals without a diagnosis who still experience symptoms, also referred to as subthreshold cases, have not been explored with network analysis in veterans. A sample of 1,050 Iraq/Afghanistan-era U.S. military veterans (851 males, mean age = 36.3, SD = 9.53) meeting current full-criteria PTSD (n = 912) and subthreshold PTSD (n = 138) were assessed with the Structured Clinical Interview for DSM-IV Disorders (SCID). Combat Exposure Scale (CES) scores were used to group the sample meeting full-criteria into high (n = 639) and low (n = 273) combat exposure subgroups. Networks were estimated using regularized partial correlation models in the R-package qgraph, and robustness tests were performed with bootnet. Frequently co-occurring symptom pairs (strong network connections) emerged between two avoidance symptoms, hypervigilance and startle response, loss of interest and detachment, as well as, detachment and restricted affect. These associations replicate findings reported across PTSD trauma types. A symptom network analysis of PTSD in a veteran population found significantly greater overall connectivity in the full-criteria PTSD group as compared to the subthreshold PTSD group. Additionally, novel findings indicate that the association between intrusive thoughts and irritability is a feature of the symptom network of veterans with high levels of combat exposure. Mean node predictability is high for PTSD symptom networks, averaging 51.5% shared variance. With the tools described here and by others, researchers can help refine diagnostic criteria for PTSD, develop more accurate measures for assessing PTSD, and eventually inform therapies that target symptoms with strong network connections to interrupt interconnected symptom complexes and promote functional recovery.

Project description:BackgroundPosttraumatic stress disorder (PTSD) is associated with sexual difficulties but the nuances of this relationship remain elusive. Research has increased in recent years, most notably following publication of several reviews in 2015.AimThis systematic review examines the relationship between PTSD and sexual difficulties in veterans/military personnel.MethodsA systematic review was conducted using PRISMA guidelines in PsycINFO and PubMed databases for studies examining a diagnosis of PTSD or PTSD severity in relation to a range of sexual difficulties. Forty-three studies were identified that met inclusion and exclusion criteria for this review.ResultsPTSD was associated with increased risk of experiencing at least one sexual difficulty. PTSD was most clearly associated with overall sexual function, sexual desire, sexual satisfaction, and sexual distress. Results were mixed for sexual arousal, orgasm function, erectile dysfunction, premature ejaculation, sexual pain, and frequency of sexual activity. PTSD symptom clusters of avoidance and negative alterations in cognition/mood were most commonly associated sexual difficulties. Few studies compared results by gender and trauma type.Clinical implicationsClinicians should inquire about sexual health in relation to PTSD symptoms and target avoidance and negative mood symptoms by incorporating sexual exposure assignments and sexual activation exercises when appropriate.Strengths & limitationsThis systematic review synthesizes an extensive literature that has grown substantially in the past 5 years and includes studies with low to moderate risk of bias. Limitations of the existing literature include challenges differentiating between PTSD and depression, inconsistent measurement of PTSD and trauma histories, inconsistent operationalization and measurement of sexual outcomes, and largely cross-sectional study designs.ConclusionPTSD is linked to a range of sexual outcomes. The current literature suggests that PTSD is associated with sexual difficulties related to both the sexual response cycle (ie, sexual desire) and one's emotional relationship to sexual activity (eg, sexual distress). More research is needed to increase confidence in findings. Bird ER, Piccirillo M, Garcia N, et al. Relationship Between Posttraumatic Stress Disorder and Sexual Difficulties: A Systematic Review of Veterans and Military Personnel. J Sex Med 2021;18:1398-1426.

Dataset Information

Epigenome-wide association study of posttraumatic stress disorder identifies novel loci in U.S. military veterans.

Publications

Epigenome-wide association study of posttraumatic stress disorder identifies novel loci in U.S. military veterans.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets