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Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans.

ABSTRACT: Posttraumatic stress disorder (PTSD) is a psychiatric disorder that can develop after experiencing traumatic events. A genome-wide association study (GWAS) design was used to identify genetic risk factors for PTSD within a multi-racial sample primarily composed of U.S. veterans.Participants were recruited at multiple medical centers, and structured interviews were used to establish diagnoses. Genotypes were generated using three Illumina platforms and imputed with global reference data to create a common set of SNPs. SNPs that increased risk for PTSD were identified with logistic regression, while controlling for gender, trauma severity, and population substructure. Analyses were run separately in non-Hispanic black (NHB; n = 949) and non-Hispanic white (NHW; n = 759) participants. Meta-analysis was used to combine results from the two subsets.SNPs within several interesting candidate genes were nominally significant. Within the NHB subset, the most significant genes were UNC13C and DSCAM. Within the NHW subset, the most significant genes were TBC1D2, SDC2 and PCDH7. In addition, PRKG1 and DDX60L were identified through meta-analysis. The top genes for the three analyses have been previously implicated in neurologic processes consistent with a role in PTSD. Pathway analysis of the top genes identified alternative splicing as the top GO term in all three analyses (FDR q < 3.5 × 10(-5)).No individual SNPs met genome-wide significance in the analyses.This multi-racial PTSD GWAS identified biologically plausible candidate genes and suggests that post-transcriptional regulation may be important to the pathology of PTSD; however, replication of these findings is needed.

SUBMITTER: Ashley-Koch AE

PROVIDER: S-EPMC4697755 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans.

Ashley-Koch Allison E AE Garrett Melanie E ME Gibson Jason J Liu Yutao Y Dennis Michelle F MF Kimbrel Nathan A NA Beckham Jean C JC Hauser Michael A MA

Journal of affective disorders 20150612

<h4>Background</h4>Posttraumatic stress disorder (PTSD) is a psychiatric disorder that can develop after experiencing traumatic events. A genome-wide association study (GWAS) design was used to identify genetic risk factors for PTSD within a multi-racial sample primarily composed of U.S. veterans.<h4>Methods</h4>Participants were recruited at multiple medical centers, and structured interviews were used to establish diagnoses. Genotypes were generated using three Illumina platforms and imputed w ...[more]

PMID: 26114229

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Project description:ImportanceMany Vietnam-era women veterans served in or near war zones and may have experienced stressful or traumatic events during their service. Although posttraumatic stress disorder (PTSD) is well studied among men who served in Vietnam, no major epidemiologic investigation of PTSD among women has been performed.ObjectivesTo assess (1) the onset and prevalence of lifetime and current PTSD for women who served during the Vietnam era, stratified by wartime location (Vietnam, near Vietnam, or the United States), and (2) the extent to which wartime location was associated with PTSD, with adjustment for demographics, service characteristics, and wartime exposures.Design, setting, and participantsSurvey of 8742 women who were active-duty military personnel in the US Armed Forces at any time from July 4, 1965, through March 28, 1973, and alive as of survey receipt as part of Department of Veterans Affairs Cooperative Study 579, HealthVIEWS. Data were obtained from mailed and telephone surveys from May 16, 2011, through August 5, 2012, and analyzed from June 26, 2013, through July 30, 2015.Main outcomes and measuresLifetime and current PTSD as measured by the PTSD module of the Composite International Diagnostic Interview, version 3.0; onset of PTSD; and wartime experiences as measured by the Women's Wartime Exposure Scale-Revised.ResultsAmong the 4219 women (48.3%) who completed the survey and a telephone interview, the weighted prevalence (95% CI) of lifetime PTSD was 20.1% (18.3%-21.8%), 11.5% (9.1%-13.9%), and 14.1% (12.4%-15.8%) for the Vietnam, near-Vietnam, and US cohorts, respectively. The weighted prevalence (95% CI) of current PTSD was 15.9% (14.3%-17.5%), 8.1% (6.0%-10.2%), and 9.1% (7.7%-10.5%) for the 3 cohorts, respectively. Few cases of PTSD among the Vietnam or near-Vietnam cohorts were attributable to premilitary onset (weighted prevalence, 2.9% [95% CI, 2.2%-3.7%] and 2.9% [95% CI, 1.7%-4.2%], respectively). Unadjusted models for lifetime and current PTSD indicated that women who served in Vietnam were more likely to meet PTSD criteria than women who mainly served in the United States (odds ratio [OR] for lifetime PTSD, 1.53 [95% CI, 1.28-1.83]; OR for current PTSD, 1.89 [95% CI, 1.53-2.33]). When we adjusted for wartime exposures, serving in Vietnam or near Vietnam did not increase the odds of having current PTSD (adjusted ORs, 1.05 [95% CI, 0.75-1.46] and 0.77 [95% CI, 0.52-1.14], respectively).Conclusions and relevanceThe prevalence of PTSD for the Vietnam cohort was higher than previously documented. Vietnam service significantly increased the odds of PTSD relative to US service; this effect appears to be associated with wartime exposures, especially sexual discrimination or harassment and job performance pressures. Results suggest long-lasting mental health effects of Vietnam-era service among women veterans.

Dataset Information

Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans.

Publications

Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans.

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