Genomics of Posttraumatic Stress Disorder in Veterans
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Psychiatric, Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 2/27/2019 |
| Start Date: | December 1, 2013 |
| End Date: | September 30, 2019 |
CSP #575B - Genomics of Posttraumatic Stress Disorder Among Veterans
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.
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.
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.
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.
Inclusion Criteria:
- Combat-exposed Veterans who participated in the Million Veteran Program.
Exclusion Criteria:
- schizophrenia
- bipolar disorder
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