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A two\u2010sample bidirectional MR analysis was conducted. Data on 1400 blood metabolites were obtained from a genome\u2010wide association study involving 8299 participants. Chronic periodontitis data were sourced from the FinnGen consortium, comprising 4784 cases and 272,252 controls. The primary analysis involved the inverse\u2010variance weighted (IVW) method. Furthermore, a metabolic pathway enrichment analysis was conducted on the metabolites identified by the IVW method. Following IVW and sensitivity analyses, 60 blood metabolites were found to be associated with chronic periodontitis. Metabolic pathway analysis suggested that these metabolites may influence chronic periodontitis through four pathways: pyrimidine metabolism, glycine, serine and threonine metabolism, arginine and proline metabolism and riboflavin metabolism. Reverse MR analysis indicated that chronic periodontitis could alter the levels of 47 blood metabolites. Pathway analysis revealed that chronic periodontitis might affect blood metabolite levels through four pathways: vitamin B6 metabolism, ether lipid metabolism, glycerophospholipid metabolism and caffeine metabolism. This study provides new insights into the pathogenesis of periodontitis, identifying potential blood biomarkers for early detection and monitoring.<\/jats:p>","DOI":"10.1111\/jcmm.70938","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T10:51:35Z","timestamp":1761907895000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring the Causal Relationship Between Blood Metabolites and Chronic Periodontitis: Insights From Genetic Causal Analysis"],"prefix":"10.1111","volume":"29","author":[{"given":"Weilun","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Stomatology, Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaxuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Nanfang Hospital Southern Medical University  Guangzhou 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