Causal associations between leisure sedentary behaviors and sleep status with frailty: insight from Mendelian randomization study

Abstract

Abstract Background Observational studies have suggested that sedentary behaviors and sleep status are associated with frailty. However, it remains unclear whether these associations are causal. Methods Using summary statistics from genome-wide association studies, we evaluated the causal effect of modifiable risk factors, including leisure sedentary behaviors and sleep status on the frailty index (FI) using two-sample univariable and multivariable Mendelian randomization (MR) analyses. Genetic correlations were tested between the correlated traits. Results We identified potential causal associations between the time spent watching television (β = 0.26, 95% confidence interval [CI]: 0.21–0.31, P = 3.98e-25), sleep duration (β = -0.18, 95%CI: -0.26, -0.10; P = 6.04e-06), and daytime napping (β = 0.29, 95%CI: 0.18–0.41, P = 2.68e-07) and the FI based on the inverse-variance-weighted method. The estimates were consistent across robust and multivariate MR analyses. Linkage disequilibrium score regression detected a genetic correlation between the time spent watching television (Rg = 0.43, P = 6.46e-48), sleep duration (Rg = -0.20, P = 5.29e-10), and daytime napping (Rg = 0.25, P = 3.34e-21) and the FI. Conclusions Genetic predispositions to time spent watching television and daytime napping were positively associated with the FI, while sleep duration was negatively associated with the FI. Our findings offer key insights into factors influencing biological aging and suggest areas for interventions to promote healthy aging and slow down the aging process.

Keywords

• Genetic correlation
• Sleep duration
• Time spent watching television
• Daytime napping
• Causality