Xing Yuhang, Pu Rui, Fu Mengdie, Wang Zhikang, Wang Zhen, Shang Xiaopeng, Yang Guoli, Jiang Zhiwei
Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China.
Stomatology 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 Province, Hangzhou, China.
Hereditas. 2025 Jan 25;162(1):8. doi: 10.1186/s41065-025-00370-2.
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.
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.
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.
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.
流行病学研究已证实人格特质神经质与身体健康之间的关系。然而，神经质与虚弱之间的关系尚未得到证实。本研究采用双向两样本孟德尔随机化（MR）方法来探究神经质与虚弱之间的因果关系。
来自英国生物银行的神经质全基因组关联研究（GWAS）数据包含489,212名参与者的12种与神经质相关的特质。遗传虚弱指数数据从英国生物银行和瑞典双胞胎基因库中提取，涉及175,226人。将与神经质和虚弱相关的独立遗传变异作为工具变量。主要使用逆方差加权（IVW）、MR-Egger、加权中位数、加权模式和MR-PRESSO进行MR分析。
MR分析显示神经质与虚弱风险之间存在正向因果关系（优势比（OR）=1.627，95%置信区间（CI）=1.538 - 1.722，P < 0.001）。在反向分析中，虚弱对较高的神经质风险有因果效应（OR = 1.270，95% CI = 1.173 - 1.375，P < 0.001）。Steiger检验表明反向因果关系并未使所确定的因果关系产生偏差。
我们的研究提供了遗传证据，表明虚弱与神经质之间存在双向因果关系。在这项双向MR研究中，与神经质相关的表型与虚弱之间存在正向因果关系，反之，虚弱也与神经质呈正相关。
