Casual associations between frailty and nine mental disorders: bidirectional Mendelian randomisation study.

IF 3.5 3区医学 Q1 PSYCHIATRY BJPsych Open Pub Date : 2025-02-03 DOI:10.1192/bjo.2024.835

Yong Zhou, Jiayue Duan, Jiayi Zhu, Yunying Huang, Tao Tu, Keke Wu, Qiuzhen Lin, Yingxu Ma, Qiming Liu

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Abstract

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 Q-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, P = 8.1 × 10^-5), anxiety (odds ratio 2.76, 95% CI 1.56-4.90, P = 5.0 × 10^-4), post-traumatic stress disorder (PTSD) (odds ratio 2.56, 95% CI 1.69-3.87, P = 9.9 × 10^-6), neuroticism (β = 0.25, 95% CI 0.11-0.38, P = 3.3 × 10^-4) and insomnia (β = 0.50, 95% CI 0.25-0.75, P = 1.1 × 10^-4). Conversely, genetic liability to MDD, neuroticism, insomnia and suicide attempt significantly increased risk of frailty (MDD: β = 0.071, 95% CI 0.033-0.110, P = 2.8 × 10^-4; neuroticism: β = 0.269, 95% CI 0.173-0.365, P = 3.4 × 10^-8; insomnia: β = 0.160, 95% CI 0.141-0.179, P = 3.2 × 10^-61; suicide attempt: β = 0.056, 95% CI 0.029-0.084, P = 3.4 × 10^-5). 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.

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虚弱和九种精神障碍之间的偶然联系：双向孟德尔随机研究。

背景：越来越多的观察性研究报道了虚弱和精神障碍之间的联系，但因果关系仍然不明确。目的：探讨虚弱与九种精神障碍之间的双向因果关系。方法：对全基因组关联研究汇总数据进行双向双样本孟德尔随机化，探讨虚弱与9种精神障碍之间的因果关系。因果效应的估计主要采用方差反加权法。应用了几次分析来验证结果。采用科克伦q检验和孟德尔随机化Egger截距评价异质性和多效性。结果：基因决定的脆弱与重度抑郁症（MDD）（优势比1.86,95% CI 1.36-2.53, P = 8.1 × 10-5）、焦虑（优势比2.76,95% CI 1.56-4.90, P = 5.0 × 10-4）、创伤后应激障碍（创伤后应激障碍）（优势比2.56,95% CI 1.69-3.87, P = 9.9 × 10-6）、神经质（β = 0.25, 95% CI 0.11-0.38, P = 3.3 × 10-4）和失眠（β = 0.50, 95% CI 0.25-0.75, P = 1.1 × 10-4）的风险增加显著相关。相反，MDD、神经质、失眠和自杀倾向的遗传倾向显著增加了虚弱的风险(MDD: β = 0.071, 95% CI 0.033-0.110, P = 2.8 × 10-4；神经质：β = 0.269, 95% CI 0.173 ~ 0.365, P = 3.4 × 10-8；失眠：β = 0.160, 95% CI 0.141 ~ 0.179, P = 3.2 × 10-61；自杀企图：β = 0.056, 95% CI 0.029-0.084, P = 3.4 × 10-5)。脆弱与自杀企图之间存在暗示性的有害关联，主观幸福感与脆弱之间存在反比关系。结论：我们的发现显示了虚弱和重度抑郁症、失眠和神经质之间的双向因果关系。此外，更脆弱的程度与焦虑和创伤后应激障碍有关，自杀企图与更脆弱有关。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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来源期刊

BJPsych Open Medicine-Psychiatry and Mental Health

CiteScore

6.30

自引率

3.70%

发文量

610

审稿时长

16 weeks

期刊介绍： Announcing the launch of BJPsych Open, an exciting new open access online journal for the publication of all methodologically sound research in all fields of psychiatry and disciplines related to mental health. BJPsych Open will maintain the highest scientific, peer review, and ethical standards of the BJPsych, ensure rapid publication for authors whilst sharing research with no cost to the reader in the spirit of maximising dissemination and public engagement. Cascade submission from BJPsych to BJPsych Open is a new option for authors whose first priority is rapid online publication with the prestigious BJPsych brand. Authors will also retain copyright to their works under a creative commons license.