{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T20:20:48Z","timestamp":1793996448021,"version":"4.8.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T00:00:00Z","timestamp":1731024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014759","name":"Medical Scientific Research Foundation of Zhejiang Province, China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014759","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Investigating the causal relationship between inflammatory cytokines and Non-alcoholic fatty liver disease(NAFLD) and identifying and quantifying the role of serum ferritin as a potential mediator.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Genetic summary statistics were derived from open genome-wide association study (GWAS) databases. We conducted a two-sample Mendelian randomization (MR) analysis to investigate the relationship between inflammatory cytokines (8,293 individuals) and NAFLD (8,434 cases, 770,180 controls). Furthermore, we used two-step MR to quantitate the proportion of the effect of serum ferritin-mediated inflammatory cytokines on NAFLD. In this study, we primarily utilized inverse-variance-weighted Mendelian randomization (MR-IVW) and reverse MR analysis methods, while other methods were also performed for sensitivity analysis, false discovery rate (FDR) &amp;lt;0.0012 as statistical significance in MR analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results indicated that high levels of Eotaxin, regulated upon activation normal T cell expressed and presumably secreted(RANTES), Interleukin-2(IL-2), macrophage migration inhibitory factor(MIF), tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) and Stem cell factor(SCF) were associated with increased risks of NAFLD, while high Cutaneous T cell-attracting chemokine(CTACK) and Interleukin-16(IL-16) levels that reduced the risk of NAFLD.The proportion of genetically predicted NAFLD mediated by ferritin was 2.1%(95% CI = 1.39%\u22125.61%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In conclusion, our study identified a causal relationship between inflammatory cytokines and NAFLD, with a small proportion of the effect mediated by ferritin, but a majority of the effect of inflammatory cytokines on NAFLD remains unclear. Further research is needed on additional risk factors as potential mediators.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2024.1437999","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T23:38:44Z","timestamp":1731022724000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetically predicted serum ferritin mediates the association between inflammatory cytokines and non-alcoholic fatty liver 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