Citation
Sipahi, Levent; Wildman, Derek E.; Aiello, Allison E.; Koenen, Karestan C.; Galea, Sandro; Abbas, Asad; & Uddin, Monica (2014). Longitudinal Epigenetic Variation of DNA Methyltransferase Genes Is Associated with Vulnerability to Post-Traumatic Stress Disorder. Psychological Medicine, 44(15), 3165-3179. PMCID: PMC4530981Abstract
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, DNMT3B and DNMT3L. 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: DNMT1 DNAm increased following trauma in PTSD cases (p = 0.001), but not controls (p = 0.067). DNMT3A and DNMT3B DNAm 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 a DNMT3B CpG site that overlaps with a TFBS involved in epigenetic regulation (p = 0.001); lower pre-trauma DNMT3B DNAm 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 resilient versus susceptible to PTSD. These distinctive DNAm differences within DNMT loci may contribute to genome-wide epigenetic profiles of PTSD.URL
http://dx.doi.org/10.1017/S0033291714000968Reference Type
Journal ArticleYear Published
2014Journal Title
Psychological MedicineAuthor(s)
Sipahi, LeventWildman, Derek E.
Aiello, Allison E.
Koenen, Karestan C.
Galea, Sandro
Abbas, Asad
Uddin, Monica