Abstract
This study aims to investigate the bidirectional causal relationship between sleep traits and frailty via 2-sample Mendelian randomization (MR) approach. Genetic data for sleep traits, including sleep duration, short sleep, long sleep, daytime naps, morning preference, and chronotype, were obtained from large-scale genome-wide association studies. Frailty Index (FI) data were sourced from a meta-analysis of European participants. MR analysis was used to examine causal relationships. Sensitivity analyses, including MR-Egger and MR-PRESSO, were conducted to assess pleiotropy, with heterogeneity tested using Cochran Q test. The Steiger test was used to rule out reverse causality. The results revealed a bidirectional causal relationship between short sleep (≤7 hours) and frailty. Short sleep was associated with a higher FI (β: 0.886, P = 1.24 × 10⁻10), and higher frailty increased the likelihood of short sleep (OR: 1.041, P = .015). No significant associations were found between FI and other sleep traits. Sensitivity analyses confirmed the robustness of these results, with no evidence of pleiotropy or heterogeneity. The Steiger test confirmed the absence of reverse causality. This study demonstrates a strong bidirectional link between short sleep and frailty, underscoring the importance of managing sleep disturbances to prevent frailty in older adults. Monitoring and addressing sleep issues may play a key role in improving health outcomes in aging populations.