Polygenic Risk and Exposure Severity Predict Trajectories of PTSD: A Prospective Cohort Study.

Posttraumatic stress disorder (PTSD) is persistent over time, thus identifying risk factors for chronic PTSD is crucial for clinical research. Trauma exposure severity and polygenic liability are two established predictors of PTSD onset and severity, but their contributions to the long-term course of PTSD remain largely unknown. In this prospective longitudinal cohort study, we tested whether severity of trauma exposure and polygenic risk for symptoms of PTSD independently predict long-term trajectories of PTSD symptoms. Data included 49,402 observations, spanning July 2002 to December 2022, from n = 5687 World Trade Center responders who had predominately European ancestry (baseline mean age = 37.74, SD = 8.19, range = 16-75; 92.89% male). First, the best-fitting model of 20-year PTSD trajectories was determined. Next, a polygenic risk score and a sum score of traumatic exposures were included as predictors of individual differences in intercepts (initial levels) and slopes (rates of change), adjusting for demographic covariates. The polygenic risk score significantly predicted rates of change in PTSD symptoms, independent of the intercept, such that higher polygenic risk was associated with more rapid increases in the years after trauma and a steeper arch-shaped trajectory. Exposure severity predicted initial levels and rates of change in symptoms, with more pronounced effects on initial levels. These findings indicate that polygenic liability and exposure severity predict the long-term prognosis of PTSD and have the potential to inform future clinical studies in trauma-exposed populations.