Associations of polygenic risk scores with posttraumatic stress symptom trajectories following combat deployment.
Associations of polygenic risk scores with posttraumatic stress symptom trajectories following combat deployment.
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DOI：
10.1017/s0033291723000211
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发表时间：
2023-03-06
影响因子：
6.9
通讯作者：
Stein, Murray B.
中科院分区：
文献类型：
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作者：
Campbell-Sills, Laura;Papini, Santiago;Norman, Sonya B.;Choi, Karmel W.;He, Feng;Sun, Xiaoying;Kessler, Ronald C.;Ursano, Robert J.;Jain, Sonia;Stein, Murray B.
关键词：
遗传风险因素的识别可能为预防和治疗创伤后应激障碍（PTSD）提供信息。本研究评估了多基因风险评分（PRS）与战斗部署后创伤后应激症状模式的关联。欧洲血统的美国陆军士兵（n = 4900）在2012年部署到阿富汗之前和之后提供了创伤后应激症状的基因组数据和评级。潜在增长混合模型被用来模拟创伤后应激症状轨迹的参与者提供部署后的数据（n = 4353）。多项逻辑回归模型测试了轨迹成员资格与PTSD，重度抑郁症（MDD），精神分裂症，神经质，酒精使用障碍和自杀企图的PRS之间的独立关联，控制年龄，性别，血统和暴露于潜在的创伤性事件，并加权以解释轨迹分类和缺失数据的不确定性。参与者被分为低严重性（77.2%），增加严重性（10.5%），减少严重性（8.0%）和高严重性（4.3%）创伤后应激症状轨迹。标准化PTSD-PRS和MDD-PRS与高严重性与低严重性轨迹成员的更大比值相关[校正比值比和95%置信区间，1.23（1.06-1.43）和1.18（1.02-1.37））以及严重程度增加与低严重程度轨迹[分别为1.12（1.01-1.25）和1.16（1.04-1.28）]。此外，MDD-PRS与严重程度递减与低严重程度轨迹中成员的更大几率相关[1.16（1.03-1.31）]。其他相关性无统计学显著性。PTSD或MDD的高多基因风险与战斗部署后更严重的创伤后应激症状轨迹相关。PRS可以帮助对风险个体进行分层，从而使治疗和预防计划更精确地针对性。
Identification of genetic risk factors may inform the prevention and treatment of posttraumatic stress disorder (PTSD). This study evaluates the associations of polygenic risk scores (PRS) with patterns of posttraumatic stress symptoms following combat deployment. US Army soldiers of European ancestry (n = 4900) provided genomic data and ratings of posttraumatic stress symptoms before and after deployment to Afghanistan in 2012. Latent growth mixture modeling was used to model posttraumatic stress symptom trajectories among participants who provided post-deployment data (n = 4353). Multinomial logistic regression models tested independent associations between trajectory membership and PRS for PTSD, major depressive disorder (MDD), schizophrenia, neuroticism, alcohol use disorder, and suicide attempt, controlling for age, sex, ancestry, and exposure to potentially traumatic events, and weighted to account for uncertainty in trajectory classification and missing data. Participants were classified into low-severity (77.2%), increasing-severity (10.5%), decreasing-severity (8.0%), and high-severity (4.3%) posttraumatic stress symptom trajectories. Standardized PTSD-PRS and MDD-PRS were associated with greater odds of membership in the high-severity v. low-severity trajectory [adjusted odds ratios and 95% confidence intervals, 1.23 (1.06–1.43) and 1.18 (1.02–1.37), respectively] and the increasing-severity v. low-severity trajectory [1.12 (1.01–1.25) and 1.16 (1.04–1.28), respectively]. Additionally, MDD-PRS was associated with greater odds of membership in the decreasing-severity v. low-severity trajectory [1.16 (1.03–1.31)]. No other associations were statistically significant. Higher polygenic risk for PTSD or MDD is associated with more severe posttraumatic stress symptom trajectories following combat deployment. PRS may help stratify at-risk individuals, enabling more precise targeting of treatment and prevention programs.