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Genomics of Posttraumatic Stress Disorder in Veterans

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ClinicalTrials.gov Identifier: NCT02256644
Recruitment Status : Active, not recruiting
First Posted : October 3, 2014
Last Update Posted : February 25, 2019
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

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 300,000 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 20,000 participants "including 10,000 combat-exposed Veterans with PTSD as cases and 10,000 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.


Condition or disease
PTSD

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 persistent/chronic PTSD have been somewhat lower (15-20%). Studies of OEF/OIF 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 6.8% (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 (yes/no) 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 11,000 confirmed PTSD cases among the approximately 145,000 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 10,000 combat-exposed Veterans with PTSD to 10,000 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.


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Study Type : Observational
Estimated Enrollment : 20000 participants
Observational Model: Case-Control
Time Perspective: Other
Official Title: CSP #575B - Genomics of Posttraumatic Stress Disorder Among Veterans
Actual Study Start Date : December 1, 2013
Actual Primary Completion Date : August 1, 2014
Estimated Study Completion Date : September 30, 2019

Resource links provided by the National Library of Medicine


Group/Cohort
Million Veteran Program (MVP) participants
Veterans who are currently enrolled in the Million Veteran Program.



Primary Outcome Measures :
  1. PTSD diagnosis [ Time Frame: 2 years ]
    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 (yes/no) as the outcome variable.


Biospecimen Retention:   Samples With DNA
Affymetrix Axiom Biobank chip, with technical specifications including "295K tag SNPs", "260K exomic content", "65K loss-of-function SNPs & INDELs", "25K psych content", and "23K eQTL markers".


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
The investigators expect 70-80% European-American (EA) and 20-30% African American (AA) in the current study
Criteria

Inclusion Criteria:

  • Combat-exposed Veterans who participated in the Million Veteran Program.

Exclusion Criteria:

  • schizophrenia
  • bipolar disorder

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02256644


Locations
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United States, California
VA San Diego Healthcare System, San Diego, CA
San Diego, California, United States, 92161
Sponsors and Collaborators
VA Office of Research and Development
Investigators
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Study Chair: Murray B Stein, MD MPH VA San Diego Healthcare System, San Diego, CA
Study Chair: Joel Gelernter, MD VA Connecticut Healthcare System West Haven Campus, West Haven, CT

Additional Information:
Publications of Results:
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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT02256644     History of Changes
Other Study ID Numbers: 575B
First Posted: October 3, 2014    Key Record Dates
Last Update Posted: February 25, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Trauma and Stressor Related Disorders
Mental Disorders