These data highlight the role of DNA methylation as biomarkers of PTSD. The results support the role of previous candidates and uncover novel genes associated with PTSD, such as DOCK2. This study contributes to our understanding of the biological underpinnings of PTSD.

Accelerated epigenetic aging, the difference between the DNA methylation-predicted age (DNAm age) and the chronological age, is associated with a myriad of diseases. This study investigates the relationship between epigenetic aging and risk and protective factors of PTSD. Genome-wide DNA methylation analysis was performed in 211 individuals including combat-exposed Australian veterans (discovery cohort, n = 96 males) and trauma-exposed civilian males from the Grady Trauma Project (replication cohort, n = 115 males). Primary measures included the Clinician Administered PTSD Scale for DSM-5 and the Connor-Davidson Resilience Scale (CD-RISC). DNAm age prediction was performed using the validated epigenetic clock calculator. Veterans with PTSD had increased PTSD symptom severity (P-value = 3.75 × 10−34) and lower CD-RISC scores (P-value = 7.5 × 10−8) than veterans without PTSD. DNAm age was significantly correlated with the chronological age (P-value = 3.3 × 10−6), but DNAm age acceleration was not different between the PTSD and non-PTSD groups (P-value = 0.24). Evaluating potential protective factors, we found that DNAm age acceleration was significantly associated with CD-RISC resilience scores in veterans with PTSD, these results remained significant after multiple testing correction (P-value = 0.023; r = 0.32). This finding was also replicated in an independent trauma-exposed civilian cohort (P-value = 0.02; r = 0.23). Post-hoc factor analyses revealed that this association was likely driven by “self-efficacy” items within the CD-RISC (P-value = 0.015; r = 0.35). These results suggest that among individuals already suffering from PTSD, some aspects of increased resilience might come at a biological cost.