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The objective of this study is to employ Mendelian randomization techniques to clarify the association between serum iron status and sarcopenia. We conducted a bi-directional Mendelian randomization (MR) analysis to investigate the potential causal relationship between iron status and sarcopenia. MR analyses were performed using inverse variance weighted (IVW), MR-Egger, and weighted median methods. Additionally, sensitivity analyses were conducted to verify the reliability of the causal association results. Then, we harvested a combination of SNPs as an integrated proxy for iron status to perform a MVMR analysis based on IVW MVMR model. UVMR analyses based on IVW method identified causal effect of ferritin on appendicular lean mass (ALM, \u03b2\u2009=\u2009\u2212\u00a00.051, 95% CI \u2212\u00a00.072, \u2212\u00a00.031, p\u2009=\u20097.325\u2009\u00d7\u200910\n                    <jats:sup>\u201307<\/jats:sup>\n                    ). Sensitivity analyses did not detect pleiotropic effects or result fluctuation by outlying SNPs in the effect estimates of four iron status on sarcopenia-related traits. After adjusting for PA, the analysis still revealed that each standard deviation higher genetically predicted ferritin was associated with lower ALM (\u03b2\u2009=\u2009\u2212\u00a00.054, 95% CI \u2212\u00a00.092, \u2212\u00a00.015,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.006). Further, MVMR analyses determined a predominant role of ferritin (\u03b2\u2009=\u2009\u2212\u00a00.068, 95% CI \u2212\u00a00.12, \u2212\u00a00.017,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20099.658\u2009\u00d7\u200910\n                    <jats:sup>\u201303<\/jats:sup>\n                    ) in the associations of iron status with ALM. Our study revealed a causal association between serum iron status and sarcopenia, with ferritin playing a key role in this relationship. These findings contribute to our understanding of the complex interplay between iron metabolism and muscle health.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-60059-w","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T05:01:58Z","timestamp":1713762118000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Iron status and sarcopenia-related traits: a bi-directional Mendelian randomization study"],"prefix":"10.1038","volume":"14","author":[{"given":"Honggu","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yizhe","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anpei","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingbo","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoyang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,4,22]]},"reference":[{"key":"60059_CR1","doi-asserted-by":"publisher","first-page":"2636","DOI":"10.1016\/S0140-6736(19)31138-9","volume":"393","author":"AJ Cruz-Jentoft","year":"2019","unstructured":"Cruz-Jentoft, A. 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