Epigenome-wide meta-analysis of PTSD symptom severity in three military cohorts implicates DNA methylation changes in genes involved in immune system and oxidative stress

• Published in: Molecular psychiatry Vol. 27; no. 3; pp. 1720 - 1728
• Main Authors: Katrinli, Seyma, Maihofer, Adam X., Wani, Agaz H., Pfeiffer, John R., Ketema, Elizabeth, Ratanatharathorn, Andrew, Baker, Dewleen G., Boks, Marco P., Geuze, Elbert, Kessler, Ronald C., Risbrough, Victoria B., Rutten, Bart P. F., Stein, Murray B., Ursano, Robert J., Vermetten, Eric, Logue, Mark W., Nievergelt, Caroline M., Smith, Alicia K., Uddin, Monica
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-03-2022; Nature Publishing Group
• Subjects: 45/22; 45/43; 45/61; 631/208; 692/699/476; Adaptor Proteins, Signal Transducing - genetics; Behavioral Sciences; Biological Psychology; DNA methylation; DNA Methylation - genetics; Environmental factors; Epigenesis, Genetic - genetics; Epigenetics; Epigenome; Humans; Immune System; Male; Medicine; Medicine & Public Health; Meta-analysis; Military deployment; Military Personnel; Neurosciences; Oxidative stress; Oxidative Stress - genetics; Pharmacotherapy; Post traumatic stress disorder; Psychiatry; Stress Disorders, Post-Traumatic - genetics
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/s41380-021-01398-2

Epigenetic factors modify the effects of environmental factors on biological outcomes. Identification of epigenetic changes that associate with PTSD is therefore a crucial step in deciphering mechanisms of risk and resilience. In this study, our goal is to identify epigenetic signatures associated with PTSD symptom severity (PTSS) and changes in PTSS over time, using whole blood DNA methylation (DNAm) data (MethylationEPIC BeadChip) of military personnel prior to and following combat deployment. A total of 429 subjects (858 samples across 2 time points) from three male military cohorts were included in the analyses. We conducted two different meta-analyses to answer two different scientific questions: one to identify a DNAm profile of PTSS using a random effects model including both time points for each subject, and the other to identify a DNAm profile of change in PTSS conditioned on pre-deployment DNAm. Four CpGs near four genes (
F2R
,
CNPY2
,
BAIAP2L1
, and
TBXAS1
) and 88 differentially methylated regions (DMRs) were associated with PTSS. Change in PTSS after deployment was associated with 15 DMRs, of those 2 DMRs near
OTUD5
and
ELF4
were also associated with PTSS. Notably, three PTSS-associated CpGs near
F2R
,
BAIAP2L1
and
TBXAS1
also showed nominal evidence of association with change in PTSS. This study, which identifies PTSD-associated changes in genes involved in oxidative stress and immune system, provides novel evidence that epigenetic differences are associated with PTSS.