Genetic Differences between Physical Injury Patients With and Without Post-traumatic Syndrome: Focus on Secondary Findings and Potential Variants Revealed by Whole Exome Sequencing.

Objective: Sudden traumatic physical injuries often cause psychological distress, which may be associated with chronic disability. Although considerable effort has been expended to identify genetic predictors of post-traumatic stress disorder (PTSD) after traumatic events, genetic predictors of psychological distress in response to severe physical injuries have been yet to be elucidated using whole exome sequencing (WES). Here, the genetic architecture of post-traumatic syndrome (PTS), which encompasses a broad range of psychiatric disorders after traumatic events including depression, anxiety disorder, acute stress disorder, and PTSD, was explored using WES in severely physically injured patients, focusing on secondary findings and potential PTS-related variants. Methods: In total, 141 severely physically injured patients were consecutively recruited, and PTS was evaluated within 1 month of the injury. Secondary findings were analyzed according to PTS status. To identify PTS-related variants, genome-wide association analyses and the optimal sequencing kernel association test were performed. Results: Of the 141 patients, 88 (62%) experienced PTS. There were 108 disease-causing variants in severely physically injured patients. As secondary findings, the stress- and inflammation-related signaling pathways were enriched in the PTS patients, while the glucose metabolism pathway was enriched in those without PTS. However, no significant PTS-related variants were identified. Conclusion: Our findings suggest that genetic alterations in stress and inflammatory pathways might increase the likelihood of PTS immediately after severe physical injury. Future studies with larger samples and longitudinal designs are needed.