{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:41:47Z","timestamp":1790613707637,"version":"4.1.0"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T00:00:00Z","timestamp":1709596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Circulating cytokines were considered to play a critical role in the initiation and propagation of sarcopenia and frailty from observational studies. This study aimed to find the casual association between circulating cytokines and sarcopenia and frailty from a genetic perspective by two-sample Mendelian randomization (MR) analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data for 41 circulating cytokines were extracted from the genome-wide association study dataset of 8,293 European participants. Inverse-variance weighted (IVW) method, MR-Egger, and weighted median method were applied to assess the relationship of circulating cytokines with the risk of aging-related syndromes and frailty. Furthermore, MR-Egger regression was used to indicate the directional pleiotropy, and Cochran\u2019s Q test was used to verify the potential heterogeneity. The \u201cleave-one-out\u201d method was applied to visualize whether there was a causal relationship affected by only one anomalous single-nucleotide polymorphisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetic predisposition to increasing levels of interleukin-10 (IL-10), IL-12, and vascular endothelial growth factor (VEGF) was associated with the higher risk of low hand grip strength according to the IVW method [R = 1.05, 95% CI = 1.01\u20131.10, <jats:italic>P<\/jats:italic> = 0.028, false discovery rate (FDR)\u2013adjusted <jats:italic>P<\/jats:italic> = 1.000; OR = 1.03, 95% CI = 1.00\u20131.07, <jats:italic>P<\/jats:italic> = 0.042, FDR-adjusted <jats:italic>P<\/jats:italic> = 0.784; OR = 1.02, 95% CI = 1.00\u20131.05, <jats:italic>P<\/jats:italic> = 0.038, FDR-adjusted <jats:italic>P<\/jats:italic> = 0.567]. Furthermore, genetically determined higher macrophage colony-stimulating factors (M-CSFs) were associated with a lower presence of appendicular lean mass (OR = 1.01, 95% CI = 1.00\u20131.02, <jats:italic>P<\/jats:italic> = 0.003, FDR-adjusted <jats:italic>P<\/jats:italic> = 0.103). Monokine induced by interferon-\u03b3 (MIG) and tumor necrosis factor\u2013beta (TNF-\u03b2) were associated with a higher risk of frailty (OR = 1.03, 95% CI = 1.01\u20131.05, <jats:italic>P<\/jats:italic> &amp;lt; 0.0001, FDR-adjusted <jats:italic>P<\/jats:italic>\u00a0= 0.012; OR = 1.01, 95% CI = 1.00\u20131.03, <jats:italic>P<\/jats:italic> = 0.013, FDR-adjusted <jats:italic>P<\/jats:italic> = 0.259). In this study, we did not find heterogeneity and horizontal pleiotropy between the circulating cytokines and the risk of frailty and sarcopenia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Genetic predisposition to assess IL-10, IL-12, and VEGF levels was associated with a higher risk of low hand grip strength and M-CSF with the presence of appendicular lean mass. The high levels of TNF-\u03b2 and MIG were associated with a higher risk of frailty. More studies will be required to explore the molecular biological mechanisms underlying the action of inflammatory factors.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2024.1293146","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T04:25:31Z","timestamp":1709612731000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["The causal association between circulating cytokines with the risk of frailty and sarcopenia under the perspective of 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