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

BACKGROUND: Observational 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...

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Autores principales: Lin, Yanze, Wang, Xun, Yao, Wenchao, Sun, Yuanting, Zhou, Jinlei, Feng, Fabo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10637380/
https://www.ncbi.nlm.nih.gov/pubmed/37955003
http://dx.doi.org/10.3389/fendo.2023.1252968
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author Lin, Yanze
Wang, Xun
Yao, Wenchao
Sun, Yuanting
Zhou, Jinlei
Feng, Fabo
author_facet Lin, Yanze
Wang, Xun
Yao, Wenchao
Sun, Yuanting
Zhou, Jinlei
Feng, Fabo
author_sort Lin, Yanze
collection PubMed
description BACKGROUND: Observational 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. METHODS: The 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. RESULTS: IVW 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. CONCLUSION: Our 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.
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spelling pubmed-106373802023-11-11 Causality between urate levels with sarcopenia-related traits: a bi-directional Mendelian randomization study Lin, Yanze Wang, Xun Yao, Wenchao Sun, Yuanting Zhou, Jinlei Feng, Fabo Front Endocrinol (Lausanne) Endocrinology BACKGROUND: Observational 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. METHODS: The 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. RESULTS: IVW 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. CONCLUSION: Our 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. Frontiers Media S.A. 2023-10-26 /pmc/articles/PMC10637380/ /pubmed/37955003 http://dx.doi.org/10.3389/fendo.2023.1252968 Text en Copyright © 2023 Lin, Wang, Yao, Sun, Zhou and Feng https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Lin, Yanze
Wang, Xun
Yao, Wenchao
Sun, Yuanting
Zhou, Jinlei
Feng, Fabo
Causality between urate levels with sarcopenia-related traits: a bi-directional Mendelian randomization study
title Causality between urate levels with sarcopenia-related traits: a bi-directional Mendelian randomization study
title_full Causality between urate levels with sarcopenia-related traits: a bi-directional Mendelian randomization study
title_fullStr Causality between urate levels with sarcopenia-related traits: a bi-directional Mendelian randomization study
title_full_unstemmed Causality between urate levels with sarcopenia-related traits: a bi-directional Mendelian randomization study
title_short Causality between urate levels with sarcopenia-related traits: a bi-directional Mendelian randomization study
title_sort causality between urate levels with sarcopenia-related traits: a bi-directional mendelian randomization study
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10637380/
https://www.ncbi.nlm.nih.gov/pubmed/37955003
http://dx.doi.org/10.3389/fendo.2023.1252968
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