Exploring the bidirectional causality between neuroticism and frailty: a Mendelian randomization analysis
Abstract Background Epidemiological studies have confirmed the relationship between personality trait neuroticism and physical health. However, the relationship between neuroticism and frailty remains unconfirmed. This study employed a bi-directional two-sample Mendelian randomization (MR) approach...
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BMC
2025-01-01
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| Series: | Hereditas |
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| Online Access: | https://doi.org/10.1186/s41065-025-00370-2 |
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| author | Yuhang Xing Rui Pu Mengdie Fu Zhikang Wang Zhen Wang Xiaopeng Shang Guoli Yang Zhiwei Jiang |
| author_facet | Yuhang Xing Rui Pu Mengdie Fu Zhikang Wang Zhen Wang Xiaopeng Shang Guoli Yang Zhiwei Jiang |
| author_sort | Yuhang Xing |
| collection | DOAJ |
| description | Abstract Background Epidemiological studies have confirmed the relationship between personality trait neuroticism and physical health. However, the relationship between neuroticism and frailty remains unconfirmed. This study employed a bi-directional two-sample Mendelian randomization (MR) approach to investigate the causal relationship between neuroticism and frailty. Methods The neuroticism genome-wide association study (GWAS) data from the UK Biobank contained twelve neuroticism-related traits with 489,212 participants. The genetic frailty index data were extracted from the UK Biobank and Swedish TwinGene, involving 175,226 individuals. Independent genetic variants associated with neuroticism and frailty were selected as instrumental variables. Inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and MR-PRESSO were mainly used for MR analysis. Results The MR analysis showed a positive causal relationship between neuroticism and the risk of frailty (odds ratio (OR) = 1.627, 95% confidence interval (CI) = 1.538–1.722, P < 0.001). In the reverse direction, frailty had a causal effect on a higher risk of neuroticism (OR = 1.270, 95% CI = 1.173–1.375, P < 0.001). Steiger tests indicated that reverse causation did not bias the identified causal relationships. Conclusions Our study provides genetic evidence suggesting a bi-directional causal relationship between frailty and neuroticism. In this bi-directional MR study, there were positive causal relationships between neuroticism-related phenotypes and frailty, and in the reverse direction, frailty was also positively correlated with neuroticism. |
| format | Article |
| id | doaj-art-ddeb13b6b02b48ac92255fc7f69f879e |
| institution | Kabale University |
| issn | 1601-5223 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Hereditas |
| spelling | doaj-art-ddeb13b6b02b48ac92255fc7f69f879e2025-01-26T12:36:41ZengBMCHereditas1601-52232025-01-0116211910.1186/s41065-025-00370-2Exploring the bidirectional causality between neuroticism and frailty: a Mendelian randomization analysisYuhang Xing0Rui Pu1Mengdie Fu2Zhikang Wang3Zhen Wang4Xiaopeng Shang5Guoli Yang6Zhiwei Jiang7Zhejiang Provincial Center for Disease Control and PreventionStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang ProvinceStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang ProvinceStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang ProvinceZhejiang Provincial Center for Disease Control and PreventionZhejiang Provincial Center for Disease Control and PreventionStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang ProvinceStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang ProvinceAbstract Background Epidemiological studies have confirmed the relationship between personality trait neuroticism and physical health. However, the relationship between neuroticism and frailty remains unconfirmed. This study employed a bi-directional two-sample Mendelian randomization (MR) approach to investigate the causal relationship between neuroticism and frailty. Methods The neuroticism genome-wide association study (GWAS) data from the UK Biobank contained twelve neuroticism-related traits with 489,212 participants. The genetic frailty index data were extracted from the UK Biobank and Swedish TwinGene, involving 175,226 individuals. Independent genetic variants associated with neuroticism and frailty were selected as instrumental variables. Inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and MR-PRESSO were mainly used for MR analysis. Results The MR analysis showed a positive causal relationship between neuroticism and the risk of frailty (odds ratio (OR) = 1.627, 95% confidence interval (CI) = 1.538–1.722, P < 0.001). In the reverse direction, frailty had a causal effect on a higher risk of neuroticism (OR = 1.270, 95% CI = 1.173–1.375, P < 0.001). Steiger tests indicated that reverse causation did not bias the identified causal relationships. Conclusions Our study provides genetic evidence suggesting a bi-directional causal relationship between frailty and neuroticism. In this bi-directional MR study, there were positive causal relationships between neuroticism-related phenotypes and frailty, and in the reverse direction, frailty was also positively correlated with neuroticism.https://doi.org/10.1186/s41065-025-00370-2FrailtyMental disorderNeuroticismMendelian randomization |
| spellingShingle | Yuhang Xing Rui Pu Mengdie Fu Zhikang Wang Zhen Wang Xiaopeng Shang Guoli Yang Zhiwei Jiang Exploring the bidirectional causality between neuroticism and frailty: a Mendelian randomization analysis Hereditas Frailty Mental disorder Neuroticism Mendelian randomization |
| title | Exploring the bidirectional causality between neuroticism and frailty: a Mendelian randomization analysis |
| title_full | Exploring the bidirectional causality between neuroticism and frailty: a Mendelian randomization analysis |
| title_fullStr | Exploring the bidirectional causality between neuroticism and frailty: a Mendelian randomization analysis |
| title_full_unstemmed | Exploring the bidirectional causality between neuroticism and frailty: a Mendelian randomization analysis |
| title_short | Exploring the bidirectional causality between neuroticism and frailty: a Mendelian randomization analysis |
| title_sort | exploring the bidirectional causality between neuroticism and frailty a mendelian randomization analysis |
| topic | Frailty Mental disorder Neuroticism Mendelian randomization |
| url | https://doi.org/10.1186/s41065-025-00370-2 |
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