Causal relationship between neuroticism and frailty: A bidirectional Mendelian randomization study

被引:2
作者
Chen, Qingyan [1 ,2 ]
Gan, Da [3 ]
Zhang, Yingjuan [2 ]
Yan, Runlan [2 ]
Li, Bei [2 ]
Tang, Wenbin [1 ]
Han, Shuang [2 ,4 ,5 ]
Gao, Yue [2 ,5 ]
机构
[1] Zhejiang Chinese Med Univ, Clin Sch Med 4, Hangzhou 310053, Zhejiang, Peoples R China
[2] Westlake Univ, Affiliated Hangzhou Peoples Hosp 1, Sch Med, Zhejiang Key Lab Tradit Chinese Med Prevent & Trea, Zhejiang 310006, Peoples R China
[3] Nanchang Univ, Affiliated Hosp 1, Jiangxi Med Acad Nutr & Hlth Management, Jiangxi Med Coll, Nanchang 330006, Peoples R China
[4] Zhejiang Chinese Med Univ, Sch Basic Med Sci, Hangzhou 310053, Zhejiang, Peoples R China
[5] Westlake Univ, Affiliated Hangzhou Peoples Hosp 1, Sch Med, Dept Geriatr, Hangzhou 310006, Zhejiang, Peoples R China
关键词
Neuroticism; Frailty; Mendelian randomization; Causal relationship; PERSONALITY; INSTRUMENTS;
D O I
10.1016/j.jad.2024.05.105
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: Observational studies have shown that neuroticism is associated with frailty, but the causal relationship between them remains unclear. Methods: A two-sample Mendelian randomization (MR) study was conducted to explore the bidirectional causal relationship between neuroticism (n = 380,506 for the primary analysis, n = 79,004 for the validation) and frailty (n = 175,226) using publicly available genome-wide association study data. The inverse variance weighted (IVW), weighted median, and MR-Egger were used to obtain the causal estimates. Findings were verified through extensive sensitivity analyses and validated using another dataset. Multivariable MR (MVMR) analysis was performed to estimate the direct causal effects with adjustment of potential confounders. Two-step MR technique was then conducted to explore the mediators in the causal effects of neuroticism on frailty. Results: Genetically-predicted higher neuroticism score was significantly correlated with higher frailty index (IVW beta: 0.53, 95%CI: 0.48 to 0.59, P = 9.3E-83), and genetically-determined higher frailty index was significantly associated with higher neuroticism score (IVW beta: 0.28, 95%CI: 0.21 to 0.35, P = 1.3E-16). These results remained robust across sensitivity analyses and were reproducible using another dataset. The MVMR analysis indicated that the causal relationships remained significant after adjusting for the potential confounding factors. Mediation analysis revealed that depression, years of schooling, and smoking were significantly mediated the causal effects of neuroticism on frailty. Conclusions: A bidirectional causal relationship existed between neuroticism and frailty. Our findings suggested that early intervention and behavioral changes might be helpful to reduce the neuroticism levels and prevent the development of frailty.
引用
收藏
页码:71 / 78
页数:8
相关论文
共 56 条
[1]   A global reference for human genetic variation [J].
Altshuler, David M. ;
Durbin, Richard M. ;
Abecasis, Goncalo R. ;
Bentley, David R. ;
Chakravarti, Aravinda ;
Clark, Andrew G. ;
Donnelly, Peter ;
Eichler, Evan E. ;
Flicek, Paul ;
Gabriel, Stacey B. ;
Gibbs, Richard A. ;
Green, Eric D. ;
Hurles, Matthew E. ;
Knoppers, Bartha M. ;
Korbel, Jan O. ;
Lander, Eric S. ;
Lee, Charles ;
Lehrach, Hans ;
Mardis, Elaine R. ;
Marth, Gabor T. ;
McVean, Gil A. ;
Nickerson, Deborah A. ;
Wang, Jun ;
Wilson, Richard K. ;
Boerwinkle, Eric ;
Doddapaneni, Harsha ;
Han, Yi ;
Korchina, Viktoriya ;
Kovar, Christie ;
Lee, Sandra ;
Muzny, Donna ;
Reid, Jeffrey G. ;
Zhu, Yiming ;
Chang, Yuqi ;
Feng, Qiang ;
Fang, Xiaodong ;
Guo, Xiaosen ;
Jian, Min ;
Jiang, Hui ;
Jin, Xin ;
Lan, Tianming ;
Li, Guoqing ;
Li, Jingxiang ;
Li, Yingrui ;
Liu, Shengmao ;
Liu, Xiao ;
Lu, Yao ;
Ma, Xuedi ;
Tang, Meifang ;
Wang, Bo .
NATURE, 2015, 526 (7571) :68-+
[2]   A genome-wide association study of the frailty index highlights brain pathways in ageing [J].
Atkins, Janice L. ;
Jylhava, Juulia ;
Pedersen, Nancy L. ;
Magnusson, Patrik K. ;
Lu, Yi ;
Wang, Yunzhang ;
Hagg, Sara ;
Melzer, David ;
Williams, Dylan M. ;
Pilling, Luke C. .
AGING CELL, 2021, 20 (09)
[3]   The impact of personality traits on the course of frailty [J].
Bos, Elizabeth G. T. ;
Douairi, Jamila ;
Kok, Rob M. M. ;
Koolhoven, Isis ;
Rius Ottenheim, Nathaly ;
Rhebergen, Didi ;
Oude Voshaar, Richard C. C. .
CLINICAL GERONTOLOGIST, 2025, 48 (01) :141-148
[4]   Meta-analysis and Mendelian randomization: A review [J].
Bowden, Jack ;
Holmes, Michael, V .
RESEARCH SYNTHESIS METHODS, 2019, 10 (04) :486-496
[5]   Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator [J].
Bowden, Jack ;
Smith, George Davey ;
Haycock, Philip C. ;
Burgess, Stephen .
GENETIC EPIDEMIOLOGY, 2016, 40 (04) :304-314
[6]   Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression [J].
Bowden, Jack ;
Smith, George Davey ;
Burgess, Stephen .
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2015, 44 (02) :512-525
[7]   Mendelian Randomization Analysis With Multiple Genetic Variants Using Summarized Data [J].
Burgess, Stephen ;
Butterworth, Adam ;
Thompson, Simon G. .
GENETIC EPIDEMIOLOGY, 2013, 37 (07) :658-665
[8]   Using Item Response Theory for the Development of a New Short Form of the Eysenck Personality Questionnaire-Revised [J].
Colledani, Daiana ;
Anselmi, Pasquale ;
Robusto, Egidio .
FRONTIERS IN PSYCHOLOGY, 2018, 9
[9]   Neuroticism as a Predictor of Frailty in Old Age: A Genetically Informative Approach [J].
Danielsdottir, Hilda Bjork ;
Jylhava, Juulia ;
Hagg, Sara ;
Lu, Yi ;
Colodro-Conde, Lucia ;
Martin, Nicholas G. ;
Pedersen, Nancy L. ;
Mosing, Miriam A. ;
Lehto, Kelli .
PSYCHOSOMATIC MEDICINE, 2019, 81 (09) :799-807
[10]   Association between frailty and depression: A bidirectional Mendelian randomization study [J].
Deng, Ming-Gang ;
Liu, Fang ;
Liang, Yuehui ;
Wang, Kai ;
Nie, Jia-Qi ;
Liu, Jiewei .
SCIENCE ADVANCES, 2023, 9 (38)