Exploring the causal link between circulating cytokines and sarcopenia traits: A Mendelian randomization analysis

Wang Di; Yang Luyao; Yang Chengwei; Anu M Valtonen; Kulmala Juha-Pekka; Gao Ying

doi:10.1002/tox.24206

Exploring the causal link between circulating cytokines and sarcopenia traits: A Mendelian randomization analysis

Environ Toxicol. 2024 Mar 7. doi: 10.1002/tox.24206. Online ahead of print.

Authors

Wang Di¹, Yang Luyao¹, Yang Chengwei², Anu M Valtonen³, Kulmala Juha-Pekka⁴, Gao Ying¹

Affiliations

¹ Department of Sports Science, College of Education, Zhejiang University, Hangzhou, China.
² Faculty of Sports and Exercise Science, University of Malaya, Kuala Lumpur, Malaysia.
³ School of Rehabilitation and Examination, Metropolia University of Applied Sciences, Finland.
⁴ Motion Analysis Laboratory, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

PMID: 38450985
DOI: 10.1002/tox.24206

Abstract

Background: Previous observational studies have linked circulating cytokines to sarcopenia, but their causal relationship remains unclear. This study employed Mendelian Randomization (MR) to investigate the causal links between circulating cytokines and sarcopenia-related traits using genetic data.

Methods: A two-sample bidirectional MR analysis was conducted using data from individuals of European ancestry, utilizing genome-wide association studies (GWAS) statistics. The study selected instrumental single nucleotide polymorphisms (SNPs) significantly associated with circulating cytokines and applied multiple MR methods, including inverse variance weighted (IVW), Weighted Median, MR-Egger, Weighted Mode, Simple Mode, and MR-PRESSO. The traits analyzed were appendicular lean mass (ALM) and grip strength. Heterogeneity, robustness, and consistency of results were assessed using Cochran's Q statistic, MR-Egger regression, and "leave-one-out" sensitivity analyses.

Results: The IVM-MR analysis showed a casual association between genetically predicted circulating levels of interleukin-16 and both ALM and grip strength (ALM: OR = 0.990, 95% CI: 0.980-1.000, p = .049; grip strength: OR = 0.971, 95% CI: 0.948-0.995, p = .020). Additionally, interferon-gamma-induced protein 10 (IP-10), interleukin-1-beta (IL-1β), and hepatocyte growth factor (HGF) were correlated with ALM and vascular endothelial growth factor (VEGF), interleukin-12 (IL-12), and interleukin-5 (IL-5) with grip strength. Comparable results were confirmed via the MR-Egger, Weighted Median, Weighted Mode, and Simple Mode methods. Sensitivity analysis showed no horizontal pleiotropy to bias the causal estimates.

Conclusion: The results suggest a significant causal effect of inflammatory cytokines on sarcopenia, offering new avenues for therapeutic target development. However, the study's focus on a European ancestry cohort limits its generalizability to other populations. Future research should aim to include diverse ethnic groups to validate and broaden these findings, thereby enhancing our understanding of sarcopenia's mechanisms in a global context.

Keywords: Mendelian randomization; appendicular lean mass; circulating cytokines; grip strength; inflammatory cytokines; sarcopenia.

Abstract

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