DNA methylation from germline cells in veterans with PTSD

Divya Mehta; Elise S Pelzer; Dagmar Bruenig; Bruce Lawford; Sarah McLeay; Charles P Morris; John N Gibson; Ross McD Young; Joanne Voisey; PTSD Initiative

doi:10.1016/j.jpsychires.2019.06.001

DNA methylation from germline cells in veterans with PTSD

J Psychiatr Res. 2019 Sep:116:42-50. doi: 10.1016/j.jpsychires.2019.06.001. Epub 2019 Jun 6.

Authors

Divya Mehta¹, Elise S Pelzer², Dagmar Bruenig³, Bruce Lawford², Sarah McLeay⁴, Charles P Morris², John N Gibson⁴, Ross McD Young⁵, Joanne Voisey²; PTSD Initiative

Collaborators

PTSD Initiative:
Sarah McLeay⁶, Wendy Harvey⁶, Madeline Romaniuk⁷, Darrell Crawford⁸, David Colquhoun⁸, Ross McD Young⁷, Miriam Dwyer⁶, John Gibson⁹, Robyn O'Sullivan⁸, Graham Cooksley¹⁰, Christopher Strakosch⁸, Rachel Thomson⁸, Joanne Voisey⁷, Bruce Lawford¹¹

Affiliations

¹ School of Psychology and Counselling, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, 4059, Australia. Electronic address: divya.mehta@qut.edu.au.
² School of Biomedical Sciences, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, 4059, Australia.
³ School of Biomedical Sciences, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, 4059, Australia; Gallipoli Medical Research Institute, Greenslopes Private Hospital, Newdegate Street, Greenslopes, QLD, 4120, Australia.
⁴ Gallipoli Medical Research Institute, Greenslopes Private Hospital, Newdegate Street, Greenslopes, QLD, 4120, Australia.
⁵ School of Psychology and Counselling, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, 4059, Australia; Gallipoli Medical Research Institute, Greenslopes Private Hospital, Newdegate Street, Greenslopes, QLD, 4120, Australia.
⁶ Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Newdegate St, Greenslopes, Australia.
⁷ Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Newdegate St, Greenslopes, Australia; School of Biomedical Sciences, Faculty of Health and Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia.
⁸ Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Newdegate St, Greenslopes, Australia; School of Medicine, The University of Queensland, Herston, Queensland, Australia; Greenslopes Private Hospital, Newdegate St, Greenslopes, Queensland Faculty of Health, Queensland University of Technology, Kelvin Grove, QLD, Australia.
⁹ Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Newdegate St, Greenslopes, Australia; Greenslopes Private Hospital, Newdegate St, Greenslopes, Queensland Faculty of Health, Queensland University of Technology, Kelvin Grove, QLD, Australia.
¹⁰ Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Newdegate St, Greenslopes, Australia; School of Medicine, The University of Queensland, Herston, Queensland, Australia.
¹¹ Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Newdegate St, Greenslopes, Australia; School of Biomedical Sciences, Faculty of Health and Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia; School of Medicine, The University of Queensland, Herston, Queensland, Australia; Greenslopes Private Hospital, Newdegate St, Greenslopes, Queensland Faculty of Health, Queensland University of Technology, Kelvin Grove, QLD, Australia.

PMID: 31195163
DOI: 10.1016/j.jpsychires.2019.06.001

Abstract

In this study we investigated genome-wide sperm DNA methylation patterns in trauma-exposed Vietnam veterans. At the genome-wide level, we identified 3 CpG sites associated with PTSD in sperm including two intergenic and one CpG within the CCDC88C gene. Of those associated with PTSD in sperm at a nominal level, 1868 CpGs were also associated with PTSD in peripheral blood (5.6% overlap) including the RORA, CRHR1 and DOCK2 genes that have been previously implicated in PTSD. A total of 10 CpG sites were significantly associated with a reported history of a diagnosed mental health condition in children and reached genome-wide significance. CpGs associated with a history of a reported mental health condition in children were also enriched (90% of tested genes) for genes previously reported to be resistant to demethylation, making them strong candidates for transgenerational inheritance. In conclusion, our findings identify a unique sperm-specific DNA methylation pattern that is associated with PTSD.

Keywords: Biomarkers; Combat exposure; DNA methylation; PTSD; Sperm; Transgenerational; Veterans.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Combat Disorders / blood
Combat Disorders / metabolism*
CpG Islands
DNA Methylation / genetics*
Humans
Male
Middle Aged
Spermatozoa / metabolism*
Stress Disorders, Post-Traumatic / blood
Stress Disorders, Post-Traumatic / metabolism*
Veterans*