Kang Hee-Ju, Lee Ho-Yeon, Kim Ki-Tae, Kim Ju-Wan, Lee Ju-Yeon, Kim Sung-Wan, Kim Jung-Chul, Shin Il-Seon, Kim Namshin, Kim Jae-Min
Department of Psychiatry, Chonnam National University Medical School, Gwangju, Korea.
Department of Bioinformatics, Korea Research Institute of Bioscience and Biotechnology School of Bioscience, University of Science and Technology (UST), Daejeon, Korea.
Clin Psychopharmacol Neurosci. 2021 Nov 30;19(4):683-694. doi: 10.9758/cpn.2021.19.4.683.
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.
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.
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.
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.
突发性创伤性身体损伤常导致心理困扰，这可能与慢性残疾有关。尽管已经付出了相当大的努力来确定创伤事件后创伤后应激障碍（PTSD）的遗传预测因素，但尚未使用全外显子组测序（WES）来阐明严重身体损伤后心理困扰的遗传预测因素。在此，我们使用WES对严重身体受伤患者的创伤后综合征（PTS）的遗传结构进行了探索，PTS包括创伤事件后的一系列精神疾病，如抑郁症、焦虑症、急性应激障碍和PTSD，重点关注次要发现和潜在的PTS相关变异。
总共连续招募了141名严重身体受伤的患者，并在受伤后1个月内对PTS进行评估。根据PTS状态分析次要发现。为了识别PTS相关变异，进行了全基因组关联分析和最佳测序核关联测试。
在141名患者中，88名（62%）经历了PTS。严重身体受伤患者中有108个致病变异。作为次要发现，PTS患者中与应激和炎症相关的信号通路富集，而未患PTS的患者中糖代谢通路富集。然而，未发现显著的PTS相关变异。
我们的研究结果表明，应激和炎症通路中的基因改变可能会增加严重身体损伤后立即发生PTS的可能性。未来需要进行更大样本量和纵向设计的研究。
