Investigation of causal associations between cerebral cortical structure and Barrett's esophagus: insights from Mendelian randomization and meta-analysis.

Background: Barrett's esophagus (BE) is a precancerous condition often associated with esophageal adenocarcinoma, influenced by both genetic and environmental factors. However, there is controversy regarding the causal relationship between cerebral cortical structures and BE, with recent studies suggesting a potential neurobiological component to its multifactorial etiology. This study aims to clarify this relationship by utilizing Mendelian randomization (MR) analysis to investigate the potential causal effects of cortical structure variations on BE risk. Methods: Comprehensive MR analyses was utilized to examine the potential causal associations between variations in cerebral cortical structure, specifically cortical thickness (TH) and surface area (SA), and the susceptibility to developing BE. Data were obtained from two genome-wide association study (GWAS) repositories. Instrumental variables were chosen using rigorous criteria, and the analysis was enhanced by employing inverse variance weighting and three additional methods, as well as conducting sensitivity analyses to evaluate the reliability of our results. In the validation stage, we used meta-analysis to combine the effect sizes to obtain robust causal relationships. Results: Initial MR findings indicated significant associations between cortical structural features in several specific regions and BE. The meta-analysis confirmed a consistent negative correlation with BE for increased cortical TH in the supramarginal and pars orbitalis regions, and a positive correlation for increased SA in the middle temporal region. Additional initial positive findings did not maintain significance in the meta-analysis, suggesting the need for cautious interpretation and further validation. Conclusions: Our study underscores the gastrointestinal-brain axis hypothesis, identifying cortical structure integrity as a potential modifier of BE risk, highlighting the importance of considering neurobiological factors in its pathogenesis. Understanding these associations could have significant clinical implications, particularly in developing targeted interventions to modify BE risk based on neurological pathways.