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| Association between sleep and frailty: a Mendelian randomization study |
| YANG Yudan1, YANG Hong1, LUO Peiyang2, SONG Jie1, SUN Xiaohui1, YE Ding1, MAO Yingying1, LI Jiayu1
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1. School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China;
2. Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China |
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Abstract Objective To examine the association between sleep and frailty using the bidirectional two-sample Mendelian randomization (MR) approach, so as to provide the basis for the prevention and intervention of frailty. Methods The data on single nucleotide polymorphisms (SNP) related to sleep duration, insomnia and morning chronotype were collected from genome-wide association studies (GWAS) and meta-analysis of GWAS, involving 446 118, 1 331 010 and 697 828 participants, respectively. The frailty was evaluated using the frailty index, and the relevant SNP data were collected from a meta-analysis of GWAS involving 175 226 participants. A bidirectional MR analysis was performed using the inverse-variance weighted method. Sensitivity analyses employed the weighted median method, the maximum likelihood-based method, the MR-Egger regression, and the MR-PRESSO test. Results Forward MR analysis showed that longer sleep duration (β=-0.170, 95%CI: -0.255 to -0.085) and morning chronotype (β=-0.036, 95%CI: -0.058 to -0.014) decreased the risk of frailty, while insomnia increased the risk of frailty (β=0.167, 95%CI: 0.149-0.184). Reverse MR analysis showed that frailty increased the risk of insomnia (OR=1.645, 95%CI: 1.278-2.117). Both bidirectional MR results were robust, which excluded the impact of heterogeneity and horizontal pleiotropy. Conclusion Sleep duration, insomnia, and morning chronotype are associated with frailty.
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Received: 30 May 2024
Revised: 27 August 2024
Published: 13 December 2024
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