Casual associations between frailty and nine mental disorders: bidirectional Mendelian randomisation study
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-sam...
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Cambridge University Press
2025-03-01
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| Series: | BJPsych Open |
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| Online Access: | https://www.cambridge.org/core/product/identifier/S2056472424008354/type/journal_article |
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| author | Yong Zhou Jiayue Duan Jiayi Zhu Yunying Huang Tao Tu Keke Wu Qiuzhen Lin Yingxu Ma Qiming Liu |
| author_facet | Yong Zhou Jiayue Duan Jiayi Zhu Yunying Huang Tao Tu Keke Wu Qiuzhen Lin Yingxu Ma Qiming Liu |
| author_sort | Yong Zhou |
| collection | DOAJ |
| description | 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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| format | Article |
| id | doaj-art-71bd1ce5ca0041b184aef9e4ea559661 |
| institution | Kabale University |
| issn | 2056-4724 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | BJPsych Open |
| spelling | doaj-art-71bd1ce5ca0041b184aef9e4ea5596612025-02-03T07:02:27ZengCambridge University PressBJPsych Open2056-47242025-03-011110.1192/bjo.2024.835Casual associations between frailty and nine mental disorders: bidirectional Mendelian randomisation studyYong Zhou0https://orcid.org/0000-0003-4016-0917Jiayue Duan1Jiayi Zhu2Yunying Huang3Tao Tu4Keke Wu5Qiuzhen Lin6Yingxu Ma7Qiming Liu8Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaDepartment of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, ChinaBackground 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. https://www.cambridge.org/core/product/identifier/S2056472424008354/type/journal_articleDepressive disordersgeneticsgenomicssuicidepsychological disorders |
| spellingShingle | Yong Zhou Jiayue Duan Jiayi Zhu Yunying Huang Tao Tu Keke Wu Qiuzhen Lin Yingxu Ma Qiming Liu Casual associations between frailty and nine mental disorders: bidirectional Mendelian randomisation study BJPsych Open Depressive disorders genetics genomics suicide psychological disorders |
| title | Casual associations between frailty and nine mental disorders: bidirectional Mendelian randomisation study |
| title_full | Casual associations between frailty and nine mental disorders: bidirectional Mendelian randomisation study |
| title_fullStr | Casual associations between frailty and nine mental disorders: bidirectional Mendelian randomisation study |
| title_full_unstemmed | Casual associations between frailty and nine mental disorders: bidirectional Mendelian randomisation study |
| title_short | Casual associations between frailty and nine mental disorders: bidirectional Mendelian randomisation study |
| title_sort | casual associations between frailty and nine mental disorders bidirectional mendelian randomisation study |
| topic | Depressive disorders genetics genomics suicide psychological disorders |
| url | https://www.cambridge.org/core/product/identifier/S2056472424008354/type/journal_article |
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