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

•GWAS for PTSD was conducted in a sample of primarily Iraq/Afghanistan veterans.•GWAS was performed in NHB and NHW subsets, and a meta-analysis combining the two.•Several candidate genes with biologic relevance to PTSD were nominally significant.•Pathway analysis implicated alternative splicing in PTSD pathophysiology.•Limited evidence for replication of previous PTSD GWAS hits was observed.

BackgroundPosttraumatic 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.MethodsParticipants 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.ResultsSNPs 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).LimitationsNo individual SNPs met genome-wide significance in the analyses.ConclusionsThis 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.