Causality between urate levels with sarcopenia-related traits: a bi-directional Mendelian randomization study

Frontiers in Endocrinology

Endocrinology

Fabo Feng¹  Yanze Lin²  Wenchao Yao³  Yuanting Sun⁴  Jinlei Zhou⁵  Xun Wang⁵ 

[1] Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China;Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China;Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China;Department of Orthopaedics, the First People’s Hospital of Chun’an County, Hangzhou, Zhejiang, China;Graduate School, Hunan University of Chinese Medicine, Changsha, China;Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China;

关键词: urate levels;    hand grip strength;    LEAN MASS;    sarcopenia;    causal relationship;    mendelian randomization;   

DOI  :  10.3389/fendo.2023.1252968

 received in 2023-07-04, accepted in 2023-10-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundObservational studies have suggested associations between serum urate levels and sarcopenia, but the causality underlying this correlation remains uncertain. The principal objective of this study is to investigate a causal relationship of serum urate levels with sarcopenia-related traits (hand grip strength, lean mass, walking pace) using bidirectional two-sample Mendelian randomization (MR) approach. The utilization of MR methodology serves to minimize bias caused by reverse causality and confounding factors from observational studies.MethodsThe summary statistics of serum urate levels were derived from a cohort consisting of 288,659 individuals participating in CKDGen study. The parameters of right-hand grip strength (N=461,089), left-hand grip strength (N=461,026), appendicular lean mass (ALM) (N=450,243), whole-body lean mass(N=454,850),right-leg fat-free mass(FFM;N=454,835),left-leg FFM(N=454,805), right-arm FFM(N=454,753),left-arm FFM(N=454,672) and walking pace (N=459,915)were sourced from the UK Biobank. MR analysis was conducted utilizing inverse variance weighted (IVW), weighted median, and MR-Egger to evaluate causality. Sensitivity analysis was performed using Cochran’s Q test, MR-Egger intercept test, leave-one-out analysis and the funnel plot.ResultsIVW estimates demonstrated that serum urate levels exhibited no causal association with sarcopenia-related traits. In the inverse MR investigation, we had exclusively discerned an inverse correlation between walking pace and serum urate levels. No compelling evidence had surfaced to substantiate any association of other sarcopenia-related traits with serum urate. Supplemental MR methods consistently validated the findings obtained from the primary analysis. Sensitivity analysis demonstrated the robustness of findings.ConclusionOur MR study revealed the absence of the bidirectional causal relationship between serum urate levels and sarcopenia. It is imperative to acknowledge that advanced age and an individual’s health status are pivotal determinants influencing urate level and the initiation and advancement of sarcopenia. However, it is worth underscoring that these aspects remain unexamined within the purview of this study. Thus, future investigations should delve deeper into these intricate facets.

【 授权许可】

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Copyright © 2023 Lin, Wang, Yao, Sun, Zhou and Feng