Journal
JOURNAL OF AFFECTIVE DISORDERS
Volume 184, Issue -, Pages 225-234Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jad.2015.03.049
Keywords
Posttraumatic stress disorder; Combat exposure; Genome-wide association study; Meta-analysis; Gene*environment interaction
Categories
Funding
- Department of Veterans Affairs' (VA) Mid-Atlantic Mental Illness Research, Education, and Clinical Center (MIRECC)
- Research & Development and Mental Health Services of the Durham Veterans Affairs Medical Center
- Clinical Science Research and Development (CSR&D) Service of the VA Office of Research and Development [IK2 CX000525]
- VA CSRD
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Background: 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. Methods: Participants were recruited at multiple medical centers, and structured interviews were used to establish diagnoses. Genotypes wore 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. Results: 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 x 10(-5)). Limitations: No individual SNPs met genome-wide significance in the analyses. Conclusions: 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. (C) 2015 Elsevier B.V. All rights reserved
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