Epigenetic Meta-Analysis Across Three Civilian Cohorts Identifies NRG1 and HGS as Blood-Based Biomarkers for Post-Traumatic Stress Disorder

Abstract

Aim: Trauma exposure is a necessary, but not deterministic, contributor to post-traumatic stress disorder (PTSD). Epigenetic factors may distinguish between trauma-exposed individuals with versus without PTSD. Materials & methods: We conducted a meta-analysis of PTSD epigenome-wide association studies in trauma-exposed cohorts drawn from civilian contexts. Whole blood-derived DNA methylation levels were analyzed in 545 study participants, drawn from the three civilian cohorts participating in the PTSD working group of the Psychiatric Genomics Consortium. Results: Two CpG sites significantly associated with current PTSD in NRG1 (cg23637605) and in HGS (cg19577098). Conclusion: PTSD is associated with differential methylation, measured in blood, within HGS and NRG1 across three civilian cohorts.

Supplementary data

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Acknowledgements

The Psychiatric Genomics Consortium Post-Traumatic Stress Disorder Epigenetics Workgroup is supported by the US Army Medical Research and Materiel Command and the National Institute of Mental Health (R01MH108826). Funding for the Detroit Neighborhood Health Study was provided by NIH R01DA022720 and RC1MH088283. The authors thank the many Detroit residents who chose to participate in the Detroit Neighborhood Health Study, as well as the technical and support staff who assisted with the study. The Grady Trauma Project, which appreciates the technical support of all of the staff, volunteers and participants, is supported by the National Institutes of Mental Health (MH096764 and MH071537). The World Trade Center research is supported by the Centers for Disease Control/National Institute of Occupational Safety and Health awards 200-2011-39361, U01OH011478, U01OH010718 and U01OH010416.

Financial & competing interests disclosure

KJ Ressler has a patent US7655655 B1 – method for facilitating extinction training using D-cycloserine issued to Extinction Pharmaceuticals, a patent WO 2005016319 A2 – acute pharmacologic augmentation of psychotherapy with enhancers of learning or conditioning issued to Extinction Pharmaceuticals, a patent WO 2012106407 A2 – diagnostic and therapeutic methods and products related to anxiety disorders pending, a patent US 20140255517 A1 – managing post-traumatic stress disorder pending, and a patent US 20170296528 A1 – methods of managing conditioned fear with neurokinin receptor antagonists pending. DE Wildman is Editor in Chief of Molecular Phylogenetics and Evolution, an Elsevier Journal, for which he receives an honorarium. The remaining authors (M Uddin, A Ratanatharathorn, D Armstrong, P Kuan, AE Aiello, EJ Bromet, S Galea, KC Koenen, B Luft, CM Nievergelt and A Smith) report no biomedical financial interests or potential conflicts of interest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

KJ Ressler has a patent US7655655 B1 – method for facilitating extinction training using D-cycloserine issued to Extinction Pharmaceuticals, a patent WO 2005016319 A2 – acute pharmacologic augmentation of psychotherapy with enhancers of learning or conditioning issued to Extinction Pharmaceuticals, a patent WO 2012106407 A2 – diagnostic and therapeutic methods and products related to anxiety disorders pending, a patent US 20140255517 A1 – managing post-traumatic stress disorder pending, and a patent US 20170296528 A1 – methods of managing conditioned fear with neurokinin receptor antagonists pending. DE Wildman is Editor in Chief of Molecular Phylogenetics and Evolution, an Elsevier Journal, for which he receives an honorarium. The remaining authors (M Uddin, A Ratanatharathorn, D Armstrong, P Kuan, AE Aiello, EJ Bromet, S Galea, KC Koenen, B Luft, CM Nievergelt and A Smith) report no biomedical financial interests or potential conflicts of interest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.