Background.Epigenetic differences exist between trauma-exposed individuals with and without post-traumatic stress disorder (PTSD). It is unclear whether these epigenetic differences pre-exist, or arise following, trauma and PTSD onset.Method.In pre- and post-trauma samples from a subset of Detroit Neighborhood Health Study participants, DNA methylation (DNAm) was measured at DNA methyltransferase 1 (DNMT1),DNMT3A, DNMT3BandDNMT3L. Pre-trauma DNAm differences and changes in DNAm from pre- to post-trauma were assessed between and within PTSD cases (n = 30) and age-, gender- and trauma exposure-matched controls (n = 30). Pre-trauma DNAm was tested for association with post-trauma symptom severity (PTSS) change. Potential functional consequences of DNAm differences were explored via bioinformatic search for putative transcription factor binding sites (TFBS).Results.DNMT1DNAm increased following trauma in PTSD cases (p = 0.001), but not controls (p = 0.067).DNMT3AandDNMT3BDNAm increased following trauma in both cases (DNMT3A:p = 0.009;DNMT3B:p < 0.001) and controls (DNMT3A:p = 0.002;DNMT3B:p < 0.001). In cases only, pre-trauma DNAm was lower at aDNMT3BCpG site that overlaps with a TFBS involved in epigenetic regulation (p = 0.001); lower pre-traumaDNMT3BDNAm at this site was predictive of worsening of PTSS post-trauma (p = 0.034). Some effects were attenuated following correction for multiple hypothesis testing.Conclusions.DNAm among trauma-exposed individuals shows both longitudinal changes and pre-existing epigenetic states that differentiate individuals who are resilientversussusceptible to PTSD. These distinctive DNAm differences withinDNMTloci may contribute to genome-wide epigenetic profiles of PTSD.