An Epigenome-Wide DNA Methylation Study of PTSD and Depression in World Trade Center Responders

Details

• Personal Author:
  Bromet E ; Gonzalez A ; Guffanti G ; Koenen K ; Kotov R ; Kuan P-F ; Luft BJ ; Marsit CJ ; Waszczuk MA ; Yang X
• Description:
  Previous epigenome-wide association studies (EWAS) of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) have been inconsistent. This may be due to small sample sizes, and measurement and tissue differences. The current two EWA analyses of 473 World Trade Center responders are the largest to date for both PTSD and MDD. These analyses investigated DNA methylation patterns and biological pathways influenced by differentially methylated genes associated with each disorder. Methylation was profiled on blood samples using Illumina 450 K Beadchip. Two EWA analyses compared current versus never PTSD, and current versus never MDD, adjusting for cell types and demographic confounders. Pathway and gene set enrichment analyses were performed to understand the complex biological systems of PTSD and MDD. No significant epigenome-wide associations were found for PTSD or MDD at an FDR P<0.05. The majority of genes with differential methylation at a suggestive threshold did not overlap between the two disorders. Pathways significant in PTSD included a regulator of synaptic plasticity, oxytocin signaling, cholinergic synapse and inflammatory disease pathways, while only phosphatidylinositol signaling and cell cycle pathways emerged in MDD. The failure of the current EWA analyses to detect significant epigenome-wide associations is in contrast with disparate findings from previous, smaller EWA and candidate gene studies of PTSD and MDD. Enriched gene sets involved in several biological pathways, including stress response, inflammation and physical health, were identified in PTSD, supporting the view that multiple genes play a role in this complex disorder. [Description provided by NIOSH]
• Subjects:
  Blood Demography Emergency Responders Genetics Hematologic Tests Immune System Mental Disorders Mental Health Occupational Health Safety September 11 Terrorist Attacks

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• Keywords:
  Alkylating Agents Biological Systems Blood Samples Cell Cycle Cell Signaling Cell Type Cholinergic Receptors Demographic Characteristics Deoxyribonucleic Acids DNA Emergency Responders Genes Genetic Factors Genomics Humans Immune System Mental Disorders Methyl Compounds Post-traumatic Stress Disorder Psychological Disorders PTSD Rescue Workers Stress-related Illnesses Translational Research World Trade Center WTC

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• ISSN:
  2158-3188
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; New York ; OSHA Region 1 ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  7
• Issue:
  6
• NIOSHTIC Number:
  nn:20050254
• Citation:
  Transl Psychiatry 2017 Jun; 7(6):e1158
• Contact Point Address:
  Dr BJ Luft, Pellegrino Professor of Medicine & Director, WTC Program, State University of New York at Stony Brook, Department of Medicine, SUNY at Stony Brook, Nicolls Road, HSC T-16, Room 082A, Stony Brook, NY 11794-8166, USA
• Email:
  Benjamin.luft@stonybrookmedicine.edu
• Federal Fiscal Year:
  2017
• Performing Organization:
  State University of New York, Stony Brook
• Peer Reviewed:
  True
• Start Date:
  20120901
• Source Full Name:
  Translational Psychiatry
• End Date:
  20150831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e00183955d9000ce7e9bcac041a4152a73f66c35fc379aab4b7b178c74b81e28847e2371d838ee8860ec21f6937b2846f8228bb8d801035ee6a9a0fa8ec493ea
• Download URL:
  https://stacks.cdc.gov/view/cdc/210677/cdc_210677_DS1.pdf
• File Type:
  [PDF - 246.55 KB ]