Identifying, validating, and characterizing of PTSD-associated proteins and integration with multi-modal molecular features from blood samples of veterans and active-duty military participants, published postmortem brain regions, and summary statistics from publicly available genome-wide association studies. PTSD cases and trauma-exposed healthy controls composed of two well-characterized cohorts: Systems Biology Consortium (SBC: 340 veterans) and Fort Campbell Cohort (FCC: 180 active-duty service members). All participants had been deployed to Iraq and/or Afghanistan. The active-duty cohort included blood biomarkers and clinical features assessed longitudinally before and after deployment. Male veterans with chronic PTSD (CAPS scores ≥ 40; ≥3 months duration) and matched controls (CAPS total score < 20) were recruited into training and testing cohorts. A smaller, case-control female veteran cohort with chronic PTSD was recruited with the same inclusion criteria. Active-duty males with recent PTSD (PCL ≥ 38; 3 days before or 90–180 days post-deployment), active-duty males with subthreshold recent PTSD (PCL ≥ 22 to < 38; 3 days before or 90–180 post-deployment), and active-duty females with recent PTSD; all cohorts included matched controls (PCL < 22). Recent onset PTSD case-controls (n = 26) were a longitudinal male active-duty cohort with recent PTSD (n = 26 controls: PCL < 22 at 2 weeks pre-deployment; n = 26 cases: PCL ≥ 31 at 3 days before or 90–180 days post-deployment). The FCC Validation and FCC Subthreshold groups shared the same controls. Comparability of molecular datasets across cohorts was verified by quality control output graphs presented inFigures S1andS2. CAPS: Clinician-Administered PTSD Scale; PCL: PTSD Checklist.