TY - JOUR
T1 - Epigenome-wide association study of posttraumatic stress disorder identifies novel loci in U.S. military veterans
AU - Traumatic Stress Brain Research Study Group
AU - Montalvo-Ortiz, Janitza L.
AU - Gelernter, Joel
AU - Cheng, Zhongshan
AU - Girgenti, Matthew J.
AU - Xu, Ke
AU - Zhang, Xinyu
AU - Gopalan, Shyamalika
AU - Zhou, Hang
AU - Duman, Ronald S.
AU - Southwick, Steven M.
AU - Krystal, John H.
AU - Friedman, Matthew J.
AU - Duman, Ronald S.
AU - Girgenti, Matthew J.
AU - Krystal, John H.
AU - Montalvo-Ortiz, Janitza L.
AU - Pietrzak, Robert H.
N1 - Publisher Copyright:
© 2022, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
PY - 2022/12
Y1 - 2022/12
N2 - Posttraumatic stress disorder (PTSD) is a chronic and disabling psychiatric disorder prevalent in military veterans. Epigenetic mechanisms have been implicated in the etiology of PTSD, with DNA methylation being the most studied to identify novel molecular biomarkers associated with this disorder. We performed one of the largest single-sample epigenome-wide association studies (EWAS) of PTSD to date. Our sample included 1135 male European–American U.S. veterans who participated in the National Health and Resilience in Veterans Study (NHRVS). DNA was collected from saliva samples and the Illumina HumanMethylation EPIC BeadChip was used for the methylation analysis. PTSD was assessed using the PTSD Checklist. An EWAS was conducted using linear regression adjusted for age, cell-type proportions, first 10 principal components, and smoking status. After Bonferroni correction, we identified six genome-wide significant (GWS) CpG sites associated with past-month PTSD and three CpGs with lifetime PTSD (prange = 10−10–10−8). These CpG sites map to genes involved in immune function, transcription regulation, axonal guidance, cell signaling, and protein binding. Among these, SENP7, which is involved in transcription regulation and has been linked to risk-taking behavior and alcohol consumption in genome-wide association studies, replicated in an independent veteran cohort and was downregulated in medial orbitofrontal cortex of PTSD postmortem brain tissue. These findings suggest potential epigenetic biomarkers of PTSD that may help inform the pathophysiology of this disorder in veterans and other trauma-affected populations.
AB - Posttraumatic stress disorder (PTSD) is a chronic and disabling psychiatric disorder prevalent in military veterans. Epigenetic mechanisms have been implicated in the etiology of PTSD, with DNA methylation being the most studied to identify novel molecular biomarkers associated with this disorder. We performed one of the largest single-sample epigenome-wide association studies (EWAS) of PTSD to date. Our sample included 1135 male European–American U.S. veterans who participated in the National Health and Resilience in Veterans Study (NHRVS). DNA was collected from saliva samples and the Illumina HumanMethylation EPIC BeadChip was used for the methylation analysis. PTSD was assessed using the PTSD Checklist. An EWAS was conducted using linear regression adjusted for age, cell-type proportions, first 10 principal components, and smoking status. After Bonferroni correction, we identified six genome-wide significant (GWS) CpG sites associated with past-month PTSD and three CpGs with lifetime PTSD (prange = 10−10–10−8). These CpG sites map to genes involved in immune function, transcription regulation, axonal guidance, cell signaling, and protein binding. Among these, SENP7, which is involved in transcription regulation and has been linked to risk-taking behavior and alcohol consumption in genome-wide association studies, replicated in an independent veteran cohort and was downregulated in medial orbitofrontal cortex of PTSD postmortem brain tissue. These findings suggest potential epigenetic biomarkers of PTSD that may help inform the pathophysiology of this disorder in veterans and other trauma-affected populations.
UR - https://www.scopus.com/pages/publications/85124778714
U2 - 10.1038/s41398-022-01822-3
DO - 10.1038/s41398-022-01822-3
M3 - Article
C2 - 35177594
AN - SCOPUS:85124778714
SN - 2158-3188
VL - 12
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 65
ER -