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

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 (R2 = 2.21% and 2.77%, padj R2 = 1.89%, padj padj R2 = 1.49%, padj p = 0.048) and 52% (p = 0.04) less risk of developing PTS, and those with high social support had 60% (p = 0.008) less risk of developing DS. Overall, genetic factors influence the risk of APNS after MVC, genetic risk of distinct APNS are overlapping, and specific social determinants greatly augment genetic risk of APNS development after MVC.