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

Details

• Personal Author:
  Abbas A ; Aiello AE ; Galea S ; Koenen KC ; Sipahi L ; Uddin M ; Wildman DE
• 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. [Description provided by NIOSH]
• Subjects:
  Aging Biomarkers Environmental Exposure Epidemiology Genetics Men Mental Disorders Mental Health Occupational Health Risk Assessment Risk Factors Safety Women

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• Keywords:
  Age Groups Author Keywords: Posttraumatic Stress Disorder DNA Methylation Epigenetics Exposure Levels Humans Longitudinal Mental Disorders Post-traumatic Stress Disorder PTSD Risk Factors Susceptibility Traumatic Injuries

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• ISSN:
  0033-2917
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Michigan ; New York ; North Carolina ; OSHA Region 2 ; OSHA Region 4 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  44
• Issue:
  15
• NIOSHTIC Number:
  nn:20047859
• Citation:
  Psychol Med 2014 Nov; 44(15):3165-3179
• Contact Point Address:
  Monica Uddin, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, 3309 Scott Hall, 540 E. Canfield Ave., Detroit, MI 48201
• Email:
  monica.uddin@wayne.edu
• Federal Fiscal Year:
  2015
• Performing Organization:
  State University New York, Stony Brook
• Peer Reviewed:
  True
• Start Date:
  20120901
• Source Full Name:
  Psychological Medicine
• End Date:
  20150831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7af05ac8a8a55331de26c163ae26ab06543bae951f77bc21b3ad38c9bab519ea2feb7b96576e368f0e150ff5d7bff88b5b6ae47a3705dfce8eaa0f97874b335f
• Download URL:
  https://stacks.cdc.gov/view/cdc/202818/cdc_202818_DS1.pdf
• File Type:
  [PDF - 347.92 KB ]