Non-alcoholic fatty liver disease and colorectal adenoma/polyps: A Two-Sample Mendelian randomization study.

Abstract Background: A potential link between non-alcoholic fatty liver disease (NAFLD) and colorectal adenoma/polyps has been suggested by observational studies, which have inherent limitations that make them unsuitable for assessing causality. We designed a two-sample Mendelian randomization (MR) study to assess the causal effects of NAFLD on adenoma/polyps in the colorectum and its eight segments. Methods: Genetic instruments were utilized as proxies for NAFLD and colorectal adenoma/polyps, and those for NAFLD were described by NAFLD clinical diagnosis and percent liver fat. Genome-wide association study (GWAS) data were obtained from GWAS Catalog and FinnGen consortium. Results: In inverse-variance weighted (IVW) models, both NAFLD clinical diagnosis [odds ratio (OR) = 1.05, 95% confidence interval (CI): 1.02-1.09, false discovery rate (FDR) = 0.008] and percent liver fat (OR = 1.08, 95% CI: 1.04-1.13, FDR = 0.001) were significantly associated with colorectal adenoma/polyps, which proved to be plausible in sensitivity analysis. As for individual segments of the colorectum, the results revealed that both NAFLD clinical diagnosis (OR = 1.10, 95% CI: 1.04-1.17, FDR = 0.010) and percent liver fat (OR = 1.17, 95% CI: 1.04-1.32, FDR = 0.034) were significantly associated with rectal adenoma/polyps without heterogeneity or pleiotropy. However, NAFLD did not show significant associations with adenoma/polyps in other segments of the colorectum. Conclusion: Our finding supported a causal effect of NAFLD on colorectal adenoma/polyps, particularly those in the rectum.