Abstract
BACKGROUND: Liver cancer may be related to changes in brain structure, but clear causal evidence is lacking. This study aims to investigate the effects of different liver cancers and cerebral cortex structure using Mendelian randomization methods, focusing on their influence regarding hepatic tumors, specifically hepatocellular carcinoma (HCC) and benign liver tumors. METHODS: Leveraging GWAS data from ENIGMA and FinnGen, we prioritized hepatic tumors (HCC, benign liver tumors) among eight liver diseases to analyze their causal relationships with cortical surface area/thickness. The inverse variance weighting method was used for the primary analysis, and MR-Egger, weighted median, and other methods were used for sensitivity analysis to ensure the robustness of the results. RESULTS: After rigorous multiple testing Bonferroni correction, we identified six significant brain-liver associations with causal evidence, including three tumor-specific relationships. Precentral gyrus surface area exhibited protective effects against benign liver tumors. At the same time, the supramarginal gyrus surface area is positively linked to benign liver/bile duct neoplasms. All the findings were verified in sensitivity analysis, indicating the reliability of the results. CONCLUSION: This Mendelian randomization study establishes the first causal evidence of hepatic tumors and cerebral cortex structure. These findings provide new insights into the neurobiological mechanisms of liver disease and provide potential targets for future intervention strategies.