The association between obstructive sleep apnea and frailty traits: a bidirectional Mendelian randomization study

BACKGROUND: This study aimed to explore the causal association between obstructive sleep apnea (OSA) and frailty traits using a bidirectional two-sample Mendelian randomization (MR) analysis. METHODS: Summary data from large-scale European genome-wide association studies were used to assess the genetic link between OSA and frailty traits, including frailty index, appendicular lean mass, grip strength, and walking pace. Effect estimates were primarily evaluated using inverse-variance weighted (IVW) analysis, complemented by MR-Egger, weighted median (WM), simple mode, and weighted mode analyses. Sensitivity analyses were performed to assess heterogeneity, outliers, and horizontal pleiotropy. RESULTS: Forward MR analysis showed no significant effect of OSA on frailty traits. However, reverse MR analysis suggested that a higher frailty index was associated with an increased risk of OSA (IVW: odds ratio [OR], 1.777; 95% confidence interval [CI], 1.137–2.777; p = 0.01) based on 14 single nucleotide polymorphisms (SNPs), and a faster walking pace was identified as a protective factor against OSA (IVW: OR, 0.204; 95% CI, 0.104–0.399; p < 0.01; WM: OR, 0.368; 95% CI, 0.193–0.703; p < 0.01) based on 56 SNPs. No significant pleiotropy was detected, and sensitivity analyses confirmed the robustness of these findings. CONCLUSION: Our MR study provided evidence that frailty traits may have a causal effect on OSA in the European ancestry population, with frailty index increasing the risk and walking pace acting as a protective factor.