Bidirectional Mendelian randomization analysis of the causal association between obesity and hepatocellular carcinoma in a European population.

This study aimed to investigate the causal relationship between obesity and hepatocellular carcinoma (HCC) using bidirectional Mendelian randomization (MR). We employed a 2-sample bidirectional MR approach using genome-wide association study summary statistics from the FinnGen consortium. Body mass index (BMI) was selected as the exposure variable for the forward MR analysis, while HCC was examined as the exposure in the reverse MR analysis. We applied multiple MR methods, including inverse-variance weighted, MR-Egger, weighted median, and mode-based approaches. Sensitivity analyses, including tests for pleiotropy and heterogeneity, were performed to assess the robustness of the findings. All MR methods consistently showed no significant causal effect between BMI and HCC, nor between HCC and BMI, suggesting no robust causal relationship in either direction. Our bidirectional MR analysis provides no evidence for a causal relationship between obesity (as measured by BMI) and the risk of developing HCC, nor does it support the hypothesis that HCC causally influences BMI. These findings suggest that while obesity is a known risk factor for HCC, the causal pathways may involve factors not captured by genetic variants associated with BMI. Further research is needed to explore the underlying mechanisms linking obesity and liver cancer.