{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:27:42Z","timestamp":1785414462133,"version":"3.56.0"},"reference-count":55,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32271214"],"award-info":[{"award-number":["32271214"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32330047"],"award-info":[{"award-number":["32330047"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471593"],"award-info":[{"award-number":["82471593"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32271214"],"award-info":[{"award-number":["32271214"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["32330047"],"award-info":[{"award-number":["32330047"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82471593"],"award-info":[{"award-number":["82471593"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study","award":["SN-ZJU-SIAS-0020"],"award-info":[{"award-number":["SN-ZJU-SIAS-0020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global public health crisis, progressing to hepatic cirrhosis and hepatocellular carcinoma. This study investigated the causal role of systemic iron status in MASLD progression. Methods: A two-sample Mendelian randomization (MR) design was implemented, with genetic variants serving as instrumental variables for four core systemic iron biomarkers. Outcome data for hepatic steatosis (8785 cases; 912,105 controls) and hepatic fibrosis\/cirrhosis (3798 cases; 904,599 controls) were extracted from the FinnGen and UK Biobank databases. Multiple complementary MR methodologies and three instrumental variable selection strategies were applied to ensure robust causal inference. Results: Genetically predicted higher serum iron (odds ratio, OR: 1.42, 95% confidence interval, 95% CI: 1.34, 1.50), ferritin (OR: 1.84, 95% CI: 1.55, 2.18), and transferrin saturation (TfSat, OR: 1.24, 95% CI: 1.19, 1.30), together with lower total iron-binding capacity (TIBC, OR: 0.81, 95% CI: 0.77, 0.85), were significantly associated with increased hepatic steatosis risk (p &lt; 0.00625). Similar associations were observed for hepatic fibrosis\/cirrhosis: serum iron (OR: 1.66, 95% CI: 1.29, 2.14), ferritin (OR: 2.52, 95% CI: 1.52, 4.18), TfSat (OR: 1.40, 95% CI: 1.19, 1.63), and reduced TIBC (OR: 0.70, 95% CI: 0.60, 0.81). MR-Bayesian model averaging prioritized serum iron (MIP: 0.85, \u03b8^MACE: 0.295; PP: 0.725; \u03b8^\u03bb: 0.344) as the top-ranked factors for steatosis and TIBC (MIP: 0.604, \u03b8^MACE: \u22120.240; PP: 0.476, \u03b8^\u03bb: \u22120.358) for fibrosis\/cirrhosis. Conclusions: Elevated systemic iron status causally drives MASLD onset and progression, highlighting iron homeostasis and ferroptosis as potential targets for prevention and clinical management.<\/jats:p>","DOI":"10.3390\/metabo16060356","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T14:10:22Z","timestamp":1779718222000},"page":"356","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mendelian Randomization Analysis of Systemic Iron Status and Risk of Metabolic Dysfunction-Associated Steatotic Liver Disease"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5622-8165","authenticated-orcid":false,"given":"Wuyang","family":"Yue","sequence":"first","affiliation":[{"name":"The Second Affiliated Hospital, School of Public Health, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou 310058, China"},{"name":"School of Public Health, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5326-241X","authenticated-orcid":false,"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Public Health, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3780-3398","authenticated-orcid":false,"given":"Jinling","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Public Health, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4425-3766","authenticated-orcid":false,"given":"Jiale","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7713-6262","authenticated-orcid":false,"given":"Xinhui","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxia","family":"Min","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Zhejiang University School of Medicine, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8730-0003","authenticated-orcid":false,"given":"Fudi","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital, School of Public Health, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou 310058, China"},{"name":"Global Innovation Institute of Element Science (GIIES-JLU), The First Hospital of Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1007\/s12072-024-10704-3","article-title":"Epidemiology and Diagnosis of Metabolic Dysfunction-Associated Fatty Liver Disease","volume":"18","author":"Fouad","year":"2024","journal-title":"Hepatol. 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