衰弱与九种精神障碍之间的因果关联：双向孟德尔随机化研究
Casual associations between frailty and nine mental disorders: bidirectional Mendelian randomisation study.
作者信息
Zhou Yong, Duan Jiayue, Zhu Jiayi, Huang Yunying, Tu Tao, Wu Keke, Lin Qiuzhen, Ma Yingxu, Liu Qiming
机构信息
Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, China.
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
出版信息
BJPsych Open. 2025 Feb 3;11(2):e28. doi: 10.1192/bjo.2024.835.
BACKGROUND
An increasing number of observational studies have reported associations between frailty and mental disorders, but the causality remains ambiguous.
AIMS
To assess the bidirectional causal relationship between frailty and nine mental disorders.
METHOD
We conducted a bidirectional two-sample Mendelian randomisation on genome-wide association study summary data, to investigate causality between frailty and nine mental disorders. Causal effects were primarily estimated using inverse variance weighted method. Several secondary analyses were applied to verify the results. Cochran's -test and Mendelian randomisation Egger intercept were applied to evaluate heterogeneity and pleiotropy.
RESULTS
Genetically determined frailty was significantly associated with increased risk of major depressive disorder (MDD) (odds ratio 1.86, 95% CI 1.36-2.53, = 8.1 × 10), anxiety (odds ratio 2.76, 95% CI 1.56-4.90, = 5.0 × 10), post-traumatic stress disorder (PTSD) (odds ratio 2.56, 95% CI 1.69-3.87, = 9.9 × 10), neuroticism ( = 0.25, 95% CI 0.11-0.38, = 3.3 × 10) and insomnia ( = 0.50, 95% CI 0.25-0.75, = 1.1 × 10). Conversely, genetic liability to MDD, neuroticism, insomnia and suicide attempt significantly increased risk of frailty (MDD: = 0.071, 95% CI 0.033-0.110, = 2.8 × 10; neuroticism: = 0.269, 95% CI 0.173-0.365, = 3.4 × 10; insomnia: = 0.160, 95% CI 0.141-0.179, = 3.2 × 10; suicide attempt: = 0.056, 95% CI 0.029-0.084, = 3.4 × 10). There was a suggestive detrimental association of frailty on suicide attempt and an inverse relationship of subjective well-being on frailty.
CONCLUSIONS
Our findings show bidirectional causal associations between frailty and MDD, insomnia and neuroticism. Additionally, higher frailty levels are associated with anxiety and PTSD, and suicide attempts are correlated with increased frailty. Understanding these associations is crucial for the effective management of frailty and improvement of mental disorders.
背景
越来越多的观察性研究报告了虚弱与精神障碍之间的关联，但因果关系仍不明确。
目的
评估虚弱与九种精神障碍之间的双向因果关系。
方法
我们对全基因组关联研究的汇总数据进行了双向两样本孟德尔随机化分析，以研究虚弱与九种精神障碍之间的因果关系。主要使用逆方差加权法估计因果效应。应用了几种次要分析方法来验证结果。采用Cochran's Q检验和孟德尔随机化Egger截距来评估异质性和多效性。
结果
基因决定的虚弱与重度抑郁症（MDD）风险增加显著相关（优势比1.86，95%置信区间1.36 - 2.53，P = 8.1×10⁻⁶）、焦虑症（优势比2.76，95%置信区间1.56 - 4.90，P = 5.0×10⁻⁴）、创伤后应激障碍（PTSD）（优势比2.56，95%置信区间1.69 - 3.87，P = 9.9×10⁻⁷）、神经质（β = 0.25，95%置信区间0.11 - 0.38，P = 3.3×10⁻⁵）和失眠（β = 0.50，95%置信区间0.25 - 0.75，P = 1.1×10⁻³）。相反，MDD、神经质、失眠和自杀未遂的遗传易感性显著增加了虚弱的风险（MDD：β = 0.071，95%置信区间0.033 - 0.110，P = 2.8×10⁻⁴；神经质：β = 0.269，95%置信区间0.173 - 0.365，P = 3.4×10⁻⁵；失眠：β = 0.160，95%置信区间0.141 - 0.179，P = 3.2×10⁻⁵；自杀未遂：β = 0.056，95%置信区间0.029 - 0.084，P = 3.4×10⁻⁵）。虚弱与自杀未遂之间存在提示性的有害关联，主观幸福感与虚弱之间存在反向关系。
结论
我们的研究结果显示了虚弱与MDD、失眠和神经质之间的双向因果关联。此外，较高的虚弱水平与焦虑症和PTSD相关，自杀未遂与虚弱增加相关。了解这些关联对于有效管理虚弱和改善精神障碍至关重要。
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