Epigenomic study of Post-traumatic Stress Disorder among OIF/OEF veterans

Emerging knowledge suggests that post-traumatic stress disorder (PTSD) is causally associated with epigenetic changes although its molecular underpinnings are still largely elusive. We postulate that differentially methylated probes mined from peripheral whole blood could be candidates for potential PTSD diagnostic signatures. Working within the Systems Biology PTSD Biomarker Consortium (SBPBC), we compared 52 PTSD male veterans (CAPS > 40) and 52 age/ethnicity matched controls (CAPS < 20) and detected ~5,600 differentially methylated CpG islands (CpGI) annotated to ~2,800 differentially methylated genes (DMG). The majority (84.5%) of these DMGs was hypermethylated in PTSD veterans, and nearly 30% of those representing the focus group of the present study were differentially methylated in their promoter regions. These promoter-bound DMGs were significantly enriched in four major network-clusters comprising PTSD-associated complications, PTSD-relevant endocrine signaling, nervous system development and nervous system functions. The severity of some current PTSD symptoms was correlated with the increased risk of medical problems, which was captured in epigenetically perturbed networks associated with insulin resistance, circadian rhythm, innate immunity and telomere management. DMGs involved with addiction, fear sensitization and neurotransmissions were enriched in the networks of long term potentiation, depression and fear memory consolidation, and thereby potentially induced lasting impacts on brain. Finally, we curated a set of DMGs that co-enrich multiple PTSD-relevant networks, and we speculate that these genes are cooperative associated with PTSD risk. The present study emphasizes the need to validate these potential PTSD signatures by probing independent cross-sectional and prospective human cohorts. Working within the Systems Biology PTSD Biomarker Consortium (SBPBC), we compared 52 PTSD male veterans (CAPS > 40) and 49 age/ethnicity matched controls (CAPS < 20) and detected ~5,600 differentially methylated CpG islands (CpGI) annotated to ~2,800 differentially methylated genes (DMG).