Transcriptome analysis reveals novel genes and immune networks dysregulated in veterans with PTSD

Abstract

Background: Posttraumatic stress disorder (PTSD) is a serious condition that emerges following trauma exposure and involves long-lasting psychological suffering and health-issues. Uncovering critical genes and molecular networks is essential to understanding the biology of the disorder. We performed a genome-wide scan to identify transcriptome signatures of PTSD.

Methods: Genome-wide peripheral blood transcriptomic data from 380 service personnel were investigated. This included a discovery sample of 96 Australian Vietnam War veterans and two independent pre and post-deployment replication samples of U.S. Marines (N = 188 and N = 96).

Results: A total of 60 transcripts were differentially expressed between veterans with and without PTSD, surviving Bonferroni multiple testing correction. Genes within the cytokine-cytokine receptor interaction, Jak-STAT signaling and Toll-like receptor signaling pathways were enriched. For 49% of the genes, gene expression changes were also accompanied by DNA methylation changes. Using replication data from two U.S. Marine cohorts, we observed that of the differentially expressed genes, 71% genes also showed significant gene expression changes between pre and post-deployment. Weighted gene co-expression networks revealed two modules of genes associated with PTSD. The first module (67 genes, p-value = 6e-4) was enriched for genes within the 11p13 locus including BDNF. The second module (266 genes, p-value = 0.01) was enriched for genes in 17q11 including SLC6A4, STAT5A and STAT5B.

Conclusions: We identified novel transcriptomic loci and biological pathways for PTSD in service personnel. Network analysis revealed enrichment of loci harboring key candidate genes in PTSD. These findings highlight the role of transcriptional biomarkers in the molecular etiology of PTSD.

Keywords: Gene expression; Genome-wide; Immune; Networks; PTSD; Veterans.