Causal Association Between Gut Microbiota and Sleep Apnoea Identified by Bayesian Weighted Mendelian Randomisation

This study investigated the potential causal relationship between gut microbiota (GM) and sleep apnoea using Mendelian randomisation (MR) analysis. Summary-level genome-wide association (GWAS) data for 473 GM and sleep apnoea were obtained from the IEU Open GWAS database. A two-sample MR framework was applied to assess the potential causal effects of GM on sleep apnoea. The primary analysis was conducted using the inverse variance-weighted (IVW) method, complemented by MR-Egger regression, weighted median, weighted mode and simple mode approaches to ensure robustness. To further account for horizontal pleiotropy and weak instrument bias, Bayesian Weighted Mendelian Randomisation (BWMR) analysis was performed as a key sensitivity model. Sensitivity analyses, including heterogeneity tests and pleiotropy assessments, were conducted to evaluate the stability and reliability of the results. IVW identified 33 GM associated with sleep apnoea (p < 0.05); BWMR confirmed 24 with significant causal effects, including 10 showing negative (protective) and 14 showing positive (risk) associations. Sensitivity analyses supported robustness: MR-PRESSO indicated outlier signals in 3 GM, Cochran's Q detected heterogeneity in 5 GM, and MR-Egger intercept suggested directional pleiotropy in 3 GM; all remaining GM showed non-significant sensitivity metrics. Leave-one-out analyses showed no single SNP disproportionately influenced the estimates, reinforcing the stability of the findings. This MR study provides genetic evidence supporting a potential causal association between GM and sleep apnoea. These findings provide new insights that may inform future research and prevention strategies.