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Causal relationship between neuroticism and frailty: A bidirectional Mendelian randomization study.
Qingyan Chen1, Da Gan2, Yingjuan Zhang3
1The Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China; Zhejiang Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Senile Chronic Diseases, Department of Geriatrics, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Zhejiang 310006, China.
Journal of Affective Disorders
|May 24, 2024
Summary
Neuroticism and frailty have a two-way causal link. Addressing neuroticism through early interventions and lifestyle changes may help prevent frailty development.
Area of Science:
- Psychiatry and Gerontology
- Genetic Epidemiology
Background:
- Observational studies suggest a link between neuroticism and frailty.
- The causal direction between neuroticism and frailty remains unclear.
Purpose of the Study:
- To investigate the bidirectional causal relationship between neuroticism and frailty using Mendelian randomization.
- To explore potential mediators in the causal pathway from neuroticism to frailty.
Main Methods:
- A two-sample Mendelian randomization (MR) study utilized large-scale genome-wide association study data.
- Inverse variance weighted (IVW), weighted median, and MR-Egger methods were employed for causal effect estimation.
- Multivariable MR (MVMR) and two-step MR analyses were conducted to assess direct effects and mediation.
Main Results:
- A significant bidirectional causal relationship was confirmed between genetically predicted neuroticism and frailty.
- Higher neuroticism was associated with increased frailty, and higher frailty was linked to increased neuroticism.
- Depression, years of schooling, and smoking were identified as significant mediators.
Conclusions:
- There is a robust bidirectional causal relationship between neuroticism and frailty.
- Interventions targeting neuroticism and associated behavioral factors may help prevent frailty.
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