Ethics approval and consent to participate
All participants included in analyses of the discovery and external validation cohorts provided consent for their participation. Details on the specific IRB approval associated with each study are provided in the Supplementary Material.
Consent for publication
Not applicable
Availability of data and materials
Owing to military cohort data sharing restrictions, data from MRS I& II, Army STARRS, PRISMO, and NCPTSD-TRACTS cannot be publicly posted. For other cohorts, individual-level data from the cohorts or cohort-level summary statistics may be made available to researchers following an approved analysis proposal through the PGC Post-traumatic Stress Disorder EWAS group with agreement of the cohort PIs. For additional information on access to these data, including PI contact information for the contributing cohorts, please contact the corresponding author.
Competing interests
Murray B. Stein has in the past 3 years received consulting income from Acadia Pharmaceuticals, Aptinyx, atai Life Sciences, BigHealth, Biogen, Bionomics, BioXcel Therapeutics, Boehringer Ingelheim, Clexio, Delix Therapeutics, Eisai, EmpowerPharm, Engrail Therapeutics, Janssen, Jazz Pharmaceuticals, NeuroTrauma Sciences, PureTech Health, Sage Therapeutics, Sumitomo Pharma, and Roche/Genentech. Dr. Stein has stock options in Oxeia Biopharmaceuticals and EpiVario. He has been paid for his editorial work on Depression and Anxiety (Editor-in-Chief), Biological Psychiatry (Deputy Editor), and UpToDate (Co-Editor-in-Chief for Psychiatry). He has also received research support from NIH, Department of Veterans Affairs, and the Department of Defense. He is on the scientific advisory board for the Brain and Behavior Research Foundation and the Anxiety and Depression Association of America. Dr. Chia-Yen Chen is an employee of Biogen. Dr. Nikolaos P. Daskalakis has served on scientific advisory boards for BioVie Pharma, Circular Genomics and Sentio Solutions for unrelated work. Dr. Nicole R. Nugent is a member of the scientific advisory board for Ilumivu. Dr. Sheila Rauch support from Wounded Warrior Project (WWP), Department of Veterans Affairs (VA), National Institute of Health (NIH), McCormick Foundation, Tonix Pharmaceuticals, Woodruff Foundation, and Department of Defense (DOD). Dr. Rauch also receives royalties from Oxford University Press and American Psychological Association Press. Dr Ressler reported receiving personal consulting fees from Sage Therapeutics, Senseye, Boerhinger Ingelheim, Jazz Pharmaceuticals, and Acer, Inc. and a sponsored research grant from Alto Neuroscience outside the submitted work.
Funding
This work was supported by the National Institutes of Health (R01MD011728 to MU, DW, AEA, R01MH108826 to AKS, MWL, CMN, MU and R01MH106595 to CMN, KCK, KJR and MBS). Army STARRS was sponsored by the Department of the Army and funded under cooperative agreement number U01MH087981 with the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health (NIH/NIMH) to co-PIs Robert J. Ursano and Murray B. Stein. NCPTSD-TRACTS was supported by Translational Research Center for TBI and Stress Disorders (TRACTS), a VA Rehabilitation Research and Development Traumatic Brain Injury National Research Center (B3001-C) to CF, and RF1AG068121 to EW. DCHS was supported by the Bill and Melinda Gates Foundation (OPP 1017641). Additional support for DJS and NK was provided by the South African Medical Research Council. The BEAR cohort was supported by R01MH105379 to NRN. The PROGrESS Cohort was supported by DOD #W81XWH-11-1-0073 to SMR and by the National Center for Advancing Translational Sciences of the NIH Award #UL1TR000433 to GAM. Data collection of PRISMO was funded by the Dutch Ministry of Defense, and DNAm analyses were funded by the VIDI Award fellowship from the Netherlands Organization for Scientific Research (NWO, grant number 917.18.336 to BPFR). SK was supported by NIH BIRCWH K12HD085850. APK was supported by K23 MH112852. VBR was supported by VA Merit Award BX005872. EW was additionally supported by Merit Review Award Number I01 CX-001276-01 from the U.S. Dept. of Veterans Affairs CSRD Service.
Authors’ contributions
PGC-PTSD writing group: N.P.D., S.K., M.W.L., C.M.N., N.R.N., A.K.S., M.B.S., M.U., A.H.W., E.B.W., A.S.Z., and X.Z.
Study PI or co-PI: A.E.A., D.G.B., C.F., E.G., R.C.K., M.W.L., W.M., M.W.M., C.M.N., N.R.N., S.A.M.R., K.J.R., V.R., A.K.S., D.J.S., M.B.S., M.U., R.J.U., E.V., D.E.W., and E.J.W.
Obtained funding for studies: M.P.B., C.F., E.G., R.C.K., M.W.L., J.J.L., C.M.N., N.R.N., S.A.M.R., K.J.R., B.P.F.R., A.K.S., M.U., R.J.U., and E.V.
Clinical: C.F., E.G., J.P.H., N.K., S.A.M.R., K.J.R., M.H.V., E.V., and E.J.W.
Contributed data: C.F., J.P.H., S.K., A.P.K., I.L., A.L, J.J.L., W.M., M.W.M., C.M.N., N.R.N., S.A.M.R., A.K.S., M.B.S., M.H.V., and E.J.W.
Statistical analysis: M.P.B., L.B., C.-Y.C., S.D., S.K., A.P.K., I.L., M.W.L., A.X.M., M.S.M., C.M.N., B.P.F.R., A.K.S., C.H.V., A.H.W., E.B.W., and X.Z.
Bioinformatics: M.P.B., L.B., C.-Y.C., S.K., M.W.L., A.X.M., B.P.F.R., and X.Z.
Genomics: M.P.B., B.P.F.R., and C.H.V.
PI of the EWAS group: M.W.L., C.M.N., A.K.S., and M.U.