Polygenic risk scoring to assess genetic overlap and protective factors influencing posttraumatic stress, depression, and chronic pain after motor vehicle collision trauma

Abstract Posttraumatic stress (PTS), depressive symptoms (DS), and musculoskeletal pain (MSP) are common sequelae of trauma exposure. Although these adverse posttraumatic neuropsychiatric sequelae (APNS) are often studied separately, clinical comorbidity is high. In a cohort of European American motor vehicle collision (MVC) trauma survivors (n = 781), substantial PTS (≥33, IES-R), DS (≥26, CES-D), and MSP (≥4, 0–10 NRS) were identified via a 6-month survey. Genetic risk was estimated using polygenic risk scores (PRSs) calculated from the largest available GWAS datasets of PTSD, MDD, and back pain. We then assessed comorbidity and genetic risk influence for developing chronic PTS, DS, and MSP after MVC. Secondary analyses explored whether common social determinants of health ameliorate genetic vulnerability. We found that 6 months after MVC, nearly half 357/781 (46%) of the participants had substantial PTS, DS, and/or MSP, and overlap was common (PTS + MSP (23%), DS + MSP (18%), PTS + DS (12%)). Genetic risk predicted post-MVC outcomes. PTSD-PRSs predicted PTS and DS (R 2 = 2.21% and 2.77%, p adj