Ignite Creation Date:
2024-05-06 @ 3:18 AM
Last Modification Date:
2024-10-26 @ 11:31 AM
Study NCT ID:
NCT02256644
Status:
COMPLETED
Last Update Posted:
2023-10-19
First Post:
2014-10-01
Brief Title:
Genomics of Posttraumatic Stress Disorder in Veterans
Sponsor:
VA Office of Research and Development
Organization:
VA Office of Research and Development
Study Overview
Official Title:
CSP 575B - Genomics of Posttraumatic Stress Disorder Among Veterans
Status:
COMPLETED
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Posttraumatic Stress Disorder PTSD as a common and serious mental health condition affects about 25 of all military personnel that have served in combat People suffering from PTSD may experience traumatic flashbacks trouble sleeping and problems in their relationships This study is intended to help identify genes that influence and increase the risk of PTSD to improve ways of detecting and treating the condition in the future
Previous research has studied genes that increase the risk of PTSD but none of these have included a Veteran-only population The current study focuses on US Veterans utilizing the VA Million Veteran Program MVP database of approximately 300000 participants as of August 2014 In this context participants with PTSD are referred to as cases and Veterans without PTSD are referred to as controls
This project will be done in three stages The first stage will look at MVP-obtained data and electronic health record EHR data to implement methods for identifying combat-exposed case patients with PTSD and combat-exposed control patients without PTSD The second stage will assemble and validate a study population of 20000 participants including 10000 combat-exposed Veterans with PTSD as cases and 10000 combat-exposed Veterans without PTSD as controls The third stage will conduct genetic analyses genotyping comparing the cases to controls to identify genes associated with increased risk of developing the condition
Previous research has studied genes that increase the risk of PTSD but none of these have included a Veteran-only population The current study focuses on US Veterans utilizing the VA Million Veteran Program MVP database of approximately 300000 participants as of August 2014 In this context participants with PTSD are referred to as cases and Veterans without PTSD are referred to as controls
This project will be done in three stages The first stage will look at MVP-obtained data and electronic health record EHR data to implement methods for identifying combat-exposed case patients with PTSD and combat-exposed control patients without PTSD The second stage will assemble and validate a study population of 20000 participants including 10000 combat-exposed Veterans with PTSD as cases and 10000 combat-exposed Veterans without PTSD as controls The third stage will conduct genetic analyses genotyping comparing the cases to controls to identify genes associated with increased risk of developing the condition
Detailed Description:
Background and Objectives
Posttraumatic stress disorder PTSD is a severe sometimes disabling anxiety disorder that can develop after a potentially traumatic event involving actual or threatened death serious injury or sexual violation The diagnosis of PTSD requires symptoms for at least one month from three categories re-experiencing avoidance and increased arousal In contrast to an acute response to trauma the stress reactions of persons who develop PTSD do not resolve quickly symptoms can last for long periods of time and may increase in severity
The rate of PTSD and consequent disability is especially high among combat-exposed military Veterans Studies of Vietnam combat veterans have consistently found a lifetime PTSD prevalence of 25-30 of men although rates of persistentchronic PTSD have been somewhat lower 15-20 Studies of OEFOIF Army personnel have reported rates of PTSD in the 10 to 15 range following deployment Thomas et al 2010 These rates are much higher than the rate of PTSD in the general US population estimated to be about 68 Kessler et al 2005
PTSD has been shown to be influenced genetically and previous work has identified several possible genes that increase the risk of PTSD Although several genomewide association studies GWASs have been conducted the corresponding statistical power has been modest and none included a Veteran-only population The proposed study will address those deficiencies by conducting a well-powered case-control GWAS study in a large sample of US Veterans with PTSD as cases and psychiatrically-healthy Veterans as controls
Preliminary Data and Research Design
The study will use a case-control design nested within the VA Million Veteran Program MVP with genotype as the exposure variable and PTSD diagnosis yesno as the outcome variable The pool of potential PTSD cases will be identified initially based on self-report of a PTSD diagnosis on a previously completed self-report questionnaire collected in MVP or evidence of a PTSD diagnosis in the VA electronic health record EHR Specific validation procedures will narrow the pool to confirmed PTSD cases and controls Based on available MVP and VA EHR data the investigators estimate a currently available source population of more than 11000 confirmed PTSD cases among the approximately 145000 MVP enrollees to date By the time this project gets underway the number of available cases and controls will be even higher due to ongoing enrollment into MVP
Laboratory Methods and Statistical Analyses
This PTSD GWAS will compare 10000 combat-exposed Veterans with PTSD to 10000 combat-exposed controls A to-be-selected microarray see narrative will be employed that contains approximately 245K genomewide association markers 250K exonic markers and INDELs 70K novel loss-of-function SNPs and INDELs and 115K custom markers Genotypes will be imputed to approximately 1KG for statistical analysis and up to 50 putatively-associated SNPs that are initially imputed will be genotyped directly in the same sample
Anticipated Results and Relevance
Genetic loci affecting combat-related PTSD risk and resilience will be identified providing important information to inform therapeutic targets related to prevention and treatment
Posttraumatic stress disorder PTSD is a severe sometimes disabling anxiety disorder that can develop after a potentially traumatic event involving actual or threatened death serious injury or sexual violation The diagnosis of PTSD requires symptoms for at least one month from three categories re-experiencing avoidance and increased arousal In contrast to an acute response to trauma the stress reactions of persons who develop PTSD do not resolve quickly symptoms can last for long periods of time and may increase in severity
The rate of PTSD and consequent disability is especially high among combat-exposed military Veterans Studies of Vietnam combat veterans have consistently found a lifetime PTSD prevalence of 25-30 of men although rates of persistentchronic PTSD have been somewhat lower 15-20 Studies of OEFOIF Army personnel have reported rates of PTSD in the 10 to 15 range following deployment Thomas et al 2010 These rates are much higher than the rate of PTSD in the general US population estimated to be about 68 Kessler et al 2005
PTSD has been shown to be influenced genetically and previous work has identified several possible genes that increase the risk of PTSD Although several genomewide association studies GWASs have been conducted the corresponding statistical power has been modest and none included a Veteran-only population The proposed study will address those deficiencies by conducting a well-powered case-control GWAS study in a large sample of US Veterans with PTSD as cases and psychiatrically-healthy Veterans as controls
Preliminary Data and Research Design
The study will use a case-control design nested within the VA Million Veteran Program MVP with genotype as the exposure variable and PTSD diagnosis yesno as the outcome variable The pool of potential PTSD cases will be identified initially based on self-report of a PTSD diagnosis on a previously completed self-report questionnaire collected in MVP or evidence of a PTSD diagnosis in the VA electronic health record EHR Specific validation procedures will narrow the pool to confirmed PTSD cases and controls Based on available MVP and VA EHR data the investigators estimate a currently available source population of more than 11000 confirmed PTSD cases among the approximately 145000 MVP enrollees to date By the time this project gets underway the number of available cases and controls will be even higher due to ongoing enrollment into MVP
Laboratory Methods and Statistical Analyses
This PTSD GWAS will compare 10000 combat-exposed Veterans with PTSD to 10000 combat-exposed controls A to-be-selected microarray see narrative will be employed that contains approximately 245K genomewide association markers 250K exonic markers and INDELs 70K novel loss-of-function SNPs and INDELs and 115K custom markers Genotypes will be imputed to approximately 1KG for statistical analysis and up to 50 putatively-associated SNPs that are initially imputed will be genotyped directly in the same sample
Anticipated Results and Relevance
Genetic loci affecting combat-related PTSD risk and resilience will be identified providing important information to inform therapeutic targets related to prevention and treatment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None