Genetically Predicted Sarcopenia Traits and the Risk of Barrett's Esophagus

A growing body of cohort research suggests a link between sarcopenia and Barrett's esophagus (BE); however, a definitive causal connection has yet to be established. Consequently, this study aims to evaluate the potential causal association between sarcopenia and BE. We obtained data on single-nucleotide polymorphisms (SNPs) linked to appendicular lean mass, hand grip strength, and walking speed, as well as outcome data related to Barrett's esophagus, from publicly available genome-wide association studies (GWAS). Utilizing these datasets, we conducted a multivariable Mendelian randomization (MR) analysis to explore potential causal associations. Univariable MR revealed significant inverse associations between sarcopenia-related traits and BE risk. Specifically, higher appendicular lean mass, stronger grip strength, and faster walking pace were each associated with reduced BE risk (all <i>p</i> < 0.05). Bidirectional MR indicated no reverse causality from BE to sarcopenia. In comprehensive multivariable MR models simultaneously adjusting for BMI, smoking, alcohol intake, dietary macronutrients, vitamin D, and calcium, appendicular lean mass (OR = 0.681, <i>p</i> = 0.028) and walking pace (OR = 0.113, <i>p</i> = 0.019) remained significantly protective against BE, whereas the associations for hand grip strength were attenuated and became non-significant. Sensitivity analyses confirmed the absence of horizontal pleiotropy and showed consistent findings across MR methods. The multivariable MR analysis demonstrated a positive causal link between sarcopenia and BE, even after adjusting for confounders. However, as all GWAS datasets were from European populations, the generalizability of these findings requires further validation. Large-scale prospective studies are needed to confirm these results and evaluate whether muscle-targeted strategies can help manage this condition.