scholarly journals Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program

2021 ◽  
Vol 53 (2) ◽  
pp. 174-184
Author(s):  
Murray B. Stein ◽  
◽  
Daniel F. Levey ◽  
Zhongshan Cheng ◽  
Frank R. Wendt ◽  
...  
Keyword(s):  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Genome Wide Association ◽  
Post Traumatic Stress ◽  
Association Analyses ◽  
Genome Wide ◽  
Post Traumatic

scholarly journals Genome-Wide Association Study of Post-Traumatic Stress Disorder in Two High-Risk Populations

2017 ◽  
Vol 20 (3) ◽  
pp. 197-207 ◽  
Author(s):  
Whitney E. Melroy-Greif ◽  
Kirk C. Wilhelmsen ◽  
Rachel Yehuda ◽  
Cindy L. Ehlers
Keyword(s):  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Olfactory Receptor ◽  
Genome Wide Association Study ◽  
Stress Disorder ◽  
Genome Wide Association ◽  
Post Traumatic Stress ◽  
Genome Wide ◽  
Post Traumatic ◽  
Receptor Family

Mexican Americans (MAs) and American Indians (AIs) constitute conspicuously understudied groups with respect to risk for post-traumatic stress disorder (PTSD), especially in light of findings showing racial/ethnic differences in trauma exposure and risk for PTSD. The purpose of this study was to examine genetic influences on PTSD in two minority cohorts. A genome-wide association study (GWAS) with sum PTSD symptoms for trauma-exposed subjects was run in each cohort. Six highly correlated variants in olfactory receptor family 11 subfamily L member 1 (OR11L1) were suggestively associated with PTSD in the MA cohort. These associations remained suggestively significant after permutation testing. A signal in a nearby olfactory receptor on chromosome 1, olfactory receptor family 2 subfamily L member 13 (OR2L13), tagged by rs151319968, was nominally associated with PTSD in the AI sample. Although no variants were significantly associated after correction for multiple testing in a meta-analysis of the two cohorts, pathway analysis of the top hits showed an enrichment cluster of terms related to sensory transduction, olfactory receptor activity, G-protein coupled receptors, and membrane. As previous studies have proposed a role for olfaction in PTSD, our results indicate this influence may be partially driven by genetic variation in the olfactory system.

Genetic Approaches to Post-Traumatic Stress Disorder

2018 ◽  
Author(s):  
Guia Guffanti ◽  
Milissa L. Kaufman ◽  
Lauren A. M. Lebois ◽  
Kerry J. Ressler
Keyword(s):  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
State Of The Art ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Post Traumatic Stress ◽  
Genome Wide ◽  
Genetic Mechanisms ◽  
Post Traumatic

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder with an estimated genetic component accounting for 30%–40% of the variance contributing to risk for the disease. This chapter starts with a review of the biological hypotheses and related genetic mechanisms currently proposed to be associated with PTSD and trauma-related disorders. It will follow with a description of the state-of-the-art on the methodologies and their application to map genetic loci and identify biomarkers associated with PTSD. Finally, we will review the latest results from genome-wide association studies of genetic variants as well as those derived from the emerging fields of epigenetics and gene expression.

scholarly journals DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Aliza P. Wingo ◽  
Lynn M. Almli ◽  
Jennifer S. Stevens ◽  
Torsten Klengel ◽  
Monica Uddin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Molecular Mechanisms ◽  
Stress Disorder ◽  
Mirna Regulation ◽  
Post Traumatic Stress ◽  
Comorbid Depression ◽  
Genome Wide ◽  
Post Traumatic

Abstract DICER1 is an enzyme that generates mature microRNAs (miRNAs), which regulate gene expression post-transcriptionally in brain and other tissues and is involved in synaptic maturation and plasticity. Here, through genome-wide differential gene expression survey of post-traumatic stress disorder (PTSD) with comorbid depression (PTSD&Dep), we find that blood DICER1 expression is significantly reduced in cases versus controls, and replicate this in two independent cohorts. Our follow-up studies find that lower blood DICER1 expression is significantly associated with increased amygdala activation to fearful stimuli, a neural correlate for PTSD. Additionally, a genetic variant in the 3′ un-translated region of DICER1, rs10144436, is significantly associated with DICER1 expression and with PTSD&Dep, and the latter is replicated in an independent cohort. Furthermore, genome-wide differential expression survey of miRNAs in blood in PTSD&Dep reveals miRNAs to be significantly downregulated in cases versus controls. Together, our novel data suggest DICER1 plays a role in molecular mechanisms of PTSD&Dep through the DICER1 and the miRNA regulation pathway.

scholarly journals Possible Association of Polymorphisms in Ubiquitin Specific Peptidase 46 Gene With Post-traumatic Stress Disorder

2021 ◽  
Vol 12 ◽  
Author(s):  
Jun Ho Seo ◽  
Tae Yong Kim ◽  
Se Joo Kim ◽  
Jin Hee Choi ◽  
Hyung Seok So ◽  
...  
Keyword(s):  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Ubiquitin Proteasome System ◽  
Combat Trauma ◽  
Post Traumatic Stress ◽  
Association Analyses ◽  
Single Marker ◽  
Ubiquitin Proteasome ◽  
Post Traumatic

Introduction: Dynamic proteolysis, through the ubiquitin-proteasome system, has an important role in DNA transcription and cell cycle, and is considered to modulate cell stress response and synaptic plasticity. We investigated whether genetic variants in the ubiquitin carboxyl-terminal hydrolase 46 (USP46) would be associated with post-traumatic stress disorder (PTSD) in people with exposure to combat trauma using a case-control candidate gene association design.Methods: Korean male veterans exposed to the Vietnam War were grouped into those with (n = 128) and without (n = 128) PTSD. Seven tagging SNPs of USP46 were selected, and single-marker and haplotype-based association analyses were performed. All analyses were adjusted for sociodemographic factors and levels of combat exposure severity and alcohol problem.Results: One single-marker (rs2244291) showed nominal evidence of association with PTSD status and with the “re-experiencing” cluster, although the association was not significant after Bonferroni correction. No significant association with the other SNPs or the haplotypes was detected.Conclusion: The present finding suggests preliminarily that genetic vulnerability regarding the ubiquitin-proteasome system may be related to fear memory processes and the development of PTSD symptoms after trauma exposure. Further studies with a larger sample size will be needed to examine the role of the ubiquitin-proteasome system including USP46 in PTSD.

scholarly journals Genome-wide differentially methylated genes associated with post-traumatic stress disorder in female rape survivors

2018 ◽  
Vol 24 ◽  
Author(s):  
Jani Nöthling ◽  
Soraya Seedat ◽  
Naeemah Abrahams ◽  
Sian Hemmings
Keyword(s):  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Differential Methylation ◽  
Post Traumatic Stress ◽  
Cpg Sites ◽  
Genome Wide ◽  
Differentially Methylated Genes ◽  
Post Traumatic ◽  
Genomic Regions

Introduction: Alterations to the epigenome in response to psychological trauma have been reported as a mechanism mediating gene and environmental interaction. Differentially methylated genes involved in the biological pathways associated with the adverse phenotypic behavioural presentations in post-traumatic stress disorder (PTSD) have previously been identified. However, the majority of studies have focussed on differential methylation of single candidate genes in participants exposed to heterogeneous index traumas. The objective of this study was to identify genome-wide differences in methylation profiles of a group of women exposed to rape, with and without PTSD.Methods: Female isiZulu participants (n = 48) between 18 and 40 years of age, who reported an incident of rape within the previous 20 days, were recruited from three Thuthuzela care centres and a crisis clinic in Durban, KwaZulu-Natal. Rape-exposed participants with and without PTSD were matched on HIV status, age, childhood maltreatment and other lifetime trauma exposure, body mass index and smoking status. DNA was extracted from peripheral blood and analysed using the Illumina Epic BeadChip microarray. Logistic regression models, adjusting for multiple comparisons, were used to identify differentially methylated genes in participants with and without PTSD at 3 months post-rape.Results: Four hundred twenty-three differentially methylated genomic regions were associated with PTSD status. Paired Box 8 (PAX8), encompassing eight CpG sites (p = 9.14E-20 and Zinc Finger Protein 57 [ZFP57]) and 19 CpG sites (p = 4.84E-18) were among the top 20 genomic regions significantly associated with PTSD in this data set, which were previously found to be associated with PTSD in other traumatised cohorts.Conclusion: PAX8 may be involved in PTSD symptoms related to sleeping difficulties and ZFP57 is believed to be involved in susceptibility to stress governed by differential methylation in hippocampal cells. This is the first study, to our knowledge, to investigate genome-wide profiles of women exposed to rape in Africa. Confirmation of these findings will require replication in larger cohorts.

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