基因预测的精神障碍与虚弱之间的因果关系：一项双向多变量孟德尔随机化研究
Causal relationship between genetically predicted mental disorders and frailty: a bidirectional and multivariable mendelian randomization study.
作者信息
Sun Wenxi, Sun Ping, Tang Sijia, Wu Xiaohui, Chen Jun, Fang Yiru, Zhang Xiaobin
机构信息
Suzhou Guangji Hospital, Suzhou, Jiangsu Province, Affiliated Guangji Hospital of Soochow University, Suzhou, 215137, Jiangsu Province, China.
Qingdao Mental Health Center, Qingdao, 266034, China.
出版信息
BMC Psychiatry. 2024 Dec 23;24(1):938. doi: 10.1186/s12888-024-06409-4.
BACKGROUND
In observational studies, frailty has been strongly associated with mental disorders. However, the mechanisms underlying the association between frailty and mental disorders remain unclear.
METHODS
We conducted a two-sample Mendelian randomization (MR) study to assess the causal relationship between frailty, as measured by the frailty index (FI), and ten common mental disorders. The datasets involved European ancestry individuals and included measurements of the FI (N = 175,226), schizophrenia (SCZ; N = 320,404), major depressive disorder (MDD; N = 143,265), bipolar disorder (N = 337,199), insomnia (N = 462,341), obsessive-compulsive disorder (N = 33,925), anxiety disorders (N = 463,010), autism spectrum disorder (N = 46,351), anorexia nervosa (N = 14,477), opioid-related mental and behavioral disorders (N = 215,650), and mental and behavioral disorders due to use of other stimulants including caffeine (N = 215,570).
RESULTS
Two-sample MR analyses were performed using inverse variance weighting followed by various sensitivity and validation analyses. Genetically predicted SCZ (odds ratio [OR] = 1.019, 95% confidence interval [CI] 1.005-1.033) and MDD (OR = 1.211, 95% CI 1.092-1.343) had significant causal effects on FI. In the reverse MR analysis, we discovered that MDD was significantly and causally affected by FI (OR = 1.290, 95% CI 1.133-1.469). No causal links were identified between the FI and the other eight common mental disorders. In the Multivariable MR, the estimated MDD effect on FI is comparable to the univariate IVW estimate (OR = 1.298; 95% CI, 1.175 to 1.435), while the estimated SCZ effect on FI fails to be significant compared to the univariate estimate. The results of the sensitivity and validation analyses confirmed stabilization.
CONCLUSIONS
Our study found evidence of a causal relationship between SCZ, MDD, and frailty and explored the underlying mechanisms.
背景
在观察性研究中，衰弱与精神障碍密切相关。然而，衰弱与精神障碍之间关联的潜在机制仍不清楚。
方法
我们进行了一项两样本孟德尔随机化（MR）研究，以评估用衰弱指数（FI）衡量的衰弱与十种常见精神障碍之间的因果关系。数据集涉及欧洲血统个体，包括FI（N = 175,226）、精神分裂症（SCZ；N = 320,404）、重度抑郁症（MDD；N = 143,265）、双相情感障碍（N = 337,199）、失眠症（N = 462,341）、强迫症（N = 33,925）、焦虑症（N = 463,010）、自闭症谱系障碍（N = 46,351）、神经性厌食症（N = 14,477）、阿片类物质所致精神和行为障碍（N = 215,650）以及使用包括咖啡因在内的其他兴奋剂所致精神和行为障碍（N = 215,570）的测量值。
结果
采用逆方差加权法进行两样本MR分析，随后进行各种敏感性和验证分析。基因预测的SCZ（优势比[OR]=1.019，95%置信区间[CI]1.005 - 1.033）和MDD（OR = 1.211，95% CI 1.092 - 1.343）对FI有显著因果效应。在反向MR分析中，我们发现MDD受到FI的显著因果影响（OR = 1.290，95% CI 1.133 - 1.469）。未发现FI与其他八种常见精神障碍之间存在因果联系。在多变量MR中，估计的MDD对FI的效应与单变量IVW估计值相当（OR = 1.298；95% CI，1.175至1.435），而估计的SCZ对FI的效应与单变量估计值相比不显著。敏感性和验证分析结果证实了稳定性。
结论
我们的研究发现了SCZ、MDD与衰弱之间存在因果关系的证据，并探讨了潜在机制。
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