Associations between Metabolic Syndrome Indicators and Colon Polyps: A Mendelian Randomization Study

Area of Science:

• Genetics
• Epidemiology
• Metabolic Health

Background:

• Observational studies suggest a link between metabolic syndrome (MetS) and increased colon polyp risk.
• The causal relationship between MetS and colon polyps requires further investigation.
• Mendelian randomization (MR) offers a robust approach to explore causality.

Purpose of the Study:

• To investigate the causal association between metabolic syndrome and its components with the risk of colon polyps.
• To utilize a two-sample MR approach for robust causal inference.
• To differentiate the effects of individual MetS components on colon polyp risk.

Main Methods:

• A two-sample Mendelian randomization (MR) analysis was conducted.
• Genome-wide association study (GWAS) data for MetS components and colon polyps were sourced from public databases (IEU, MAGIC).
• Inverse variance-weighted (IVW) method was primary; MR-PRESSO and false discovery rate (FDR) correction were used for sensitivity analyses.

Main Results:

• Hypertension, hyperlipidemia, and diabetes showed no significant association with colon polyp risk.
• Positive associations were found between body mass index (BMI), body fat percentage, waist-to-hip ratio, total cholesterol (TC), triglycerides (TG), and omega-6 fatty acids with colon polyp risk.
• Negative associations were observed for high-density lipoprotein cholesterol (HDL-C), 2-hour glucose, glycated hemoglobin A1c, and the ratio of omega-6 to omega-3 fatty acids with colon polyp risk.
• Associations remained significant after FDR correction.

Conclusions:

• Obesity indicators (BMI, body fat, waist-hip ratio), elevated TC, and TG are associated with an increased risk of colon polyps.
• Higher HDL-C levels may have a protective effect against colon polyp development.
• These findings highlight specific metabolic factors influencing colon polyp risk, informing potential prevention strategies.