Nonalcoholic fatty liver disease and colorectal cancer: a two-sample bidirectional Mendelian randomization analysis.

Objective: Observational studies suggest a connection between nonalcoholic fatty liver disease (NAFLD) and colorectal cancer (CRC) risk. It, however, remains unclear whether such a connection is causal. This study aims to examine the association between NAFLD and CRC using a two-sample bidirectional Mendelian randomization (MR) method.

Methods: Summary statistics for NAFLD were obtained from four genome-wide association studies, including 8434 cases and 770 180 controls. Meanwhile, CRC and controls (1803 vs. 174 006) were collected from the FinnGen. The inverse variance weighted (IVW) method was used primarily, while sensitivity analyses were conducted via the weighted median, MR Egger method, simple mode, and weighted mode to enhance result reliability.

Results: We found a positive correlation between NAFLD and CRC by IVW method in the forward MR analysis (odds ratio = 1.270, 95% confidence interval: 1.154-1.398, P = 1.092 × 10-6). Inverse MR analysis, however, suggested that CRC may not have a causal effect on NAFLD. Besides, we observed an absence of horizontal pleiotropy and heterogeneity in this MR analysis.

Conclusion: Our forward MR study found that NAFLD may increase CRC risk. In contrast, CRC may not have a causal relationship with NAFLD. This study provides genetic evidence supporting a cause-and-effect association between NAFLD and CRC.