Longitudinal epigenetic variation of DNA methyltransferase genes associated with vulnerability to post-traumatic stress disorder (PTSD)

Details

• Alternative Title:
  Psychol Med
• Personal Author:
  Sipahi, Levent ; Wildman, Derek E. ; Aiello, Allison E. ; Koenen, Karestan C. ; Galea, Sandro ; Abbas, Asad ; Uddin, Monica
• Description:
  BACKGROUND
  
  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.
  
  METHODS
  
  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).
  
  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 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.
  
  
• Subjects:
  Adult Aged Article DNA (Cytosine-5-)-Methyltransferase DNA Methylation Epidemiology Epigenesis, Genetic Epigenetics Female Genetic Predisposition To Disease Humans Longitudinal Longitudinal Studies Male Middle Aged Posttraumatic Stress Disorder Severity Of Illness Index Stress Disorders, Post-Traumatic Susceptibility

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• Source:
  Psychol Med. 44(15):3165-3179.
• Pubmed ID:
  25065861
• Pubmed Central ID:
  PMC4530981
• Document Type:
  Journal Article
• 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
• Volume:
  44
• Issue:
  15
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:58d38360d46f4f964d4300b980b1a07b239cccc2544ec95a02197d815f49cecf
• Download URL:
  https://stacks.cdc.gov/view/cdc/32778/cdc_32778_DS1.pdf
• File Type:
  [PDF - 550.20 KB ]