Polygenic prediction of PTSD trajectories in 9/11 responders.
Polygenic prediction of PTSD trajectories in 9/11 responders.
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DOI：
10.1017/s0033291720003839
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发表时间：
2020-10-23
影响因子：
6.9
通讯作者：
Luft BJ
中科院分区：
文献类型：
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作者：
Waszczuk MA;Docherty AR;Shabalin AA;Miao J;Yang X;Kuan PF;Bromet E;Kotov R;Luft BJ
遗传学有望预测创伤后长期创伤后应激障碍（PTSD）的结果。本研究的目的是测试六种假设的多基因风险评分 (PRS) 是否能够捕捉精神疾病的遗传易感性，前瞻性地预测创伤后应激障碍 (PTSD) 的发病、严重程度和创伤暴露后 18 年的病程。参与者是世贸中心 (WTC) 灾难的 1490 名响应者（9/11 时的平均年龄 = 38.81 岁，S.D. = 8.20；93.5% 为男性；23.8% 终生诊断为与世贸中心相关的 PTSD）。从电子病历中获得了 WTC 相关 PTSD 症状的前瞻性纵向数据，并使用生长混合模型分析将其建模为 PTSD 轨迹。独立回归模型测试了六种假设的精神 PRS（PTSD-PRS、重新体验-PRS、广泛性焦虑-PRS、精神分裂症-PRS、抑郁-PRS 和神经质-PRS）是否可以预测 WTC-PTSD 结果：终生诊断、平均症状严重程度和 18 年症状轨迹。所有分析均针对人群分层、9/11 暴露严重程度和多重测试进行了调整。抑郁-PRS 预测 PTSD 诊断状态（OR 1.37，CI 1.17–1.61，调整后 p = 0.001）。除 PTSD-PRS 外，所有 PRS 均显着预测平均 PTSD 症状（β = 0.06–0.10，调整后 p < 0.05）。重新体验-PRS、广泛性焦虑-PRS 和精神分裂症-PRS 预测了高严重性 PTSD 轨迹类别（OR 1.21-1.28，调整后 p < 0.05）。最后，PRS 预测与 9/11 暴露严重程度无关，并且共同解释了 PTSD 症状的方差是暴露严重程度的 3.7 倍。精神病学 PRS 前瞻性预测了世贸中心相关的 PTSD 终生诊断、平均症状严重程度以及 9/11 灾难响应者的 18 年轨迹。总而言之，PRS 比暴露严重程度更能预测随后的 PTSD。将来，PRS 可能有助于识别可能受益于有针对性的预防方法的高危响应者。
Genetics hold promise of predicting long-term post-traumatic stress disorder (PTSD) outcomes following trauma. The aim of the current study was to test whether six hypothesized polygenic risk scores (PRSs) developed to capture genetic vulnerability to psychiatric conditions prospectively predict PTSD onset, severity, and 18-year course after trauma exposure. Participants were 1490 responders to the World Trade Center (WTC) disaster (mean age at 9/11 = 38.81 years, S.D. = 8.20; 93.5% male; 23.8% lifetime WTC-related PTSD diagnosis). Prospective longitudinal data on WTC-related PTSD symptoms were obtained from electronic medical records and modelled as PTSD trajectories using growth mixture model analysis. Independent regression models tested whether six hypothesized psychiatric PRSs (PTSD-PRS, Re-experiencing-PRS, Generalized Anxiety-PRS, Schizophrenia-PRS, Depression-PRS, and Neuroticism-PRS) are predictive of WTC-PTSD outcomes: lifetime diagnoses, average symptom severity, and 18-year symptom trajectory. All analyses were adjusted for population stratification, 9/11 exposure severity, and multiple testing. Depression-PRS predicted PTSD diagnostic status (OR 1.37, CI 1.17–1.61, adjusted p = 0.001). All PRSs, except PTSD-PRS, significantly predicted average PTSD symptoms (β = 0.06–0.10, adjusted p < 0.05). Re-experiencing-PRS, Generalized Anxiety-PRS and Schizophrenia-PRS predicted the high severity PTSD trajectory class (ORs 1.21–1.28, adjusted p < 0.05). Finally, PRSs prediction was independent of 9/11 exposure severity and jointly accounted for 3.7 times more variance in PTSD symptoms than the exposure severity. Psychiatric PRSs prospectively predicted WTC-related PTSD lifetime diagnosis, average symptom severity, and 18-year trajectory in responders to 9/11 disaster. Jointly, PRSs were more predictive of subsequent PTSD than the exposure severity. In the future, PRSs may help identify at-risk responders who might benefit from targeted prevention approaches.