Longitudinal epigenetic variation of DNA methyltransferase genes associated with vulnerability to post-traumatic stress disorder (PTSD)
Published Date:Apr 25 2014
Source:Psychol Med. 44(15):3165-3179.
Genetic Predisposition To Disease
Posttraumatic Stress Disorder
Severity Of Illness Index
Stress Disorders, Post-Traumatic
Pubmed Central ID:PMC4530981
Funding:P51 RR000165/RR/NCRR NIH HHS/United States
R01 DA022720/DA/NIDA NIH HHS/United States
R01 MH093612/MH/NIMH NIH HHS/United States
RC1 MH088283/MH/NIMH NIH HHS/United States
RC4 MH092707/MH/NIMH NIH HHS/United States
U01 OH010407/OH/NIOSH CDC HHS/United States
U01 OH010416/OH/NIOSH CDC HHS/United States
Epigenetic differences exist between trauma-exposed individuals with and without posttraumatic stress disorder (PTSD). It is unclear whether these epigenetic differences preexist, or arise following, trauma and PTSD onset.
In pre- and post-trauma samples from a subset of Detroit Neighborhood Health Study participants, DNA methylation (DNAm) was measured at 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).
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.
DNAm among trauma-exposed individuals shows both longitudinal changes and preexisting epigenetic states that differentiate individuals who are resilient vs. susceptible to PTSD. These distinctive DNAm differences within DNMT loci may contribute to genome-wide epigenetic profiles of PTSD.
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