The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.

While PTSD and comorbid PTSD/depression are indistinguishable, the findings support the existence of depression as a separate construct in the acute, but not the chronic, aftermath of trauma.

A timely determination of the risk of post-traumatic stress disorder (PTSD) is a prerequisite for efficient service delivery and prevention. We provide a risk estimate tool allowing a calculation of individuals' PTSD likelihood from early predictors. Members of the International Consortium to Predict PTSD (ICPP) shared individual participants' item-level data from ten longitudinal studies of civilian trauma survivors admitted to acute care centers in six countries. Eligible participants (N=2,473) completed an initial clinical assessment within 60 days of trauma exposure, and at least one follow-up assessment 4-15 months later. The Clinician-Administered PTSD Scale for DSM-IV (CAPS) evaluated PTSD symptom severity and diagnostic status at each assessment. Participants' education, prior lifetime trauma exposure, marital status and socio-economic status were assessed and harmonized across studies. The study's main outcome was the likelihood of a follow-up PTSD given early predictors. The prevalence of follow-up PTSD was 11.8% (9.2% for male participants and 16.4% for females). A logistic model using early PTSD symptom severity (initial CAPS total score) as a predictor produced remarkably accurate estimates of . Adding respondents' female gender, lower education, and exposure to prior interpersonal trauma to the model yielded higher PTSD likelihood estimates, with similar model accuracy (predicted vs. raw probabilities: r=0.941). The current model could be adjusted for other traumatic circumstances and accommodate risk factors not captured by the ICPP (e.g., biological, social). In line with their use in general medicine, risk estimate models can inform clinical choices in psychiatry. It is hoped that quantifying individuals' PTSD risk will be a first step towards systematic prevention of the disorder.

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