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However, the potential relationship between iron metabolism disorders and susceptibility to pneumonia remains unclear. This study explores the association between iron metabolism disorder and susceptibility to bacterial pneumonia, viral pneumonia, and sepsis. GWAS data from the FinnGen and UK biobank is used for a two\u2010sample Mendelian randomization (MR) analysis, followed by MR meta\u2010analysis. Low serum iron levels were negatively associated with the risk of bacterial pneumonia (OR, 0.85;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.04), influenza pneumonia (OR, 0.86;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.03), and sepsis (OR, 0.81;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0004). Increased transferrin saturation and decreased total iron\u2010binding capacity were linked to higher risks of bacterial pneumonia and sepsis. Elevated liver iron content correlated positively with susceptibility to bacterial pneumonia (OR, 1.11;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.007), influenza pneumonia (OR, 1.08;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.03), and sepsis (OR, 1.13;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0007), but negatively with pneumococcal pneumonia (OR, 37.62;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0013). Neutrophils mediated the impact of serum iron and transferrin saturation on susceptibility to bacterial pneumonia and sepsis. This MR study confirms that disruptions in iron metabolism, including low serum iron levels and elevated liver iron content, increase susceptibility to bacterial and viral pneumonia as well as sepsis by affecting neutrophil function and cytokine levels. The findings emphasize the need for monitoring iron metabolism indicators in high\u2010risk populations and provide valuable insights for further mechanistic research and clinical intervention.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.70422","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T02:30:12Z","timestamp":1749609012000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Genetic Susceptibility to Causal Relationship Between Iron Metabolism Disorder Involving Immunocytes and Risk of Pneumonia and Sepsis"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1342-8773","authenticated-orcid":false,"given":"Zhenchao","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Peking University Third Hospital  Beijing People's Republic of 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