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This study used a two-sample Mendelian randomization (MR) approach to evaluate the relationship between MetS and colon polyps.Methods: A two-sample MR analysis was performed using data on MetS, its indicators, and colon polyps obtained from publicly available genome-wide association studies in the Integrative Epidemiology Unit (IEU) and MAGIC databases. Outliers were removed using Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), followed by MR calculations and false discovery rate (FDR) correction. The primary analysis was conducted with the inverse variance-weighted (IVW) method.Results: The IVW results indicated no association between hypertension, hyperlipidemia, or diabetes and the risk of colon polyps. High-density lipoprotein cholesterol (HDL-C) (P=0.005), 2-hour glucose (P=0.004), glycated hemoglobin A1c (P=0.004), and the ratio of omega-6 to omega-3 fatty acids (P&lt;0.001) were negatively associated with colon polyps. Conversely, body mass index (BMI) (P&lt;0.001), body fat percentage (P=0.002), waist-to-hip ratio adjusted for BMI (P=0.001), total cholesterol (TC) (P=0.002), triglycerides (TG) (P&lt;0.001), and both omega-3 (P&lt;0.001) and omega-6 fatty acid levels (P=0.02) were positively associated with colon polyps. The relationships between these metabolic indicators and colon polyps remained significant after FDR correction.Conclusion: Obesity-related traits, TC, and TG may increase the risk of colon polyps, while HDL-C may have a protective effect.<\/jats:p>","DOI":"10.3803\/enm.2025.2379","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T07:54:00Z","timestamp":1769068440000},"page":"256-266","update-policy":"https:\/\/doi.org\/10.3803\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations between Metabolic Syndrome Indicators and Colon Polyps: A Mendelian Randomization Study"],"prefix":"10.3803","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8548-9869","authenticated-orcid":true,"given":"Dongya","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Hangzhou Red Cross Hospital, Hangzhou, 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