Comprehensive Genetic Analysis Exploring Sedentary Lifestyle, Physical Activity, and Respiratory Diseases: A Bidirectional Mendelian Randomization with over 500,000 Participants

Introduction: The association between sedentary lifestyle, physical activity, and risk of respiratory diseases is a crucial area of medical and health research. Despite numerous studies, uncertainties and controversies regarding the causal relationships persist. We utilized Mendelian randomization (MR) analysis, an advanced statistical tool, to further investigate causal links. Methods: In this study, bidirectional MR analysis was performed to determine the potential causal relationships between leisure screen time (LST), moderate-to-vigorous intensity physical activity during leisure time (MVPA), sedentary behavior at work (SBW), and 10 common respiratory diseases. Results: Aggregating outcomes from analytical assessments showed that LST was positively correlated with the risk of asthma (odds ratio [OR] = 1.22, 95% confidence interval [CI] = 1.10–1.34, p = 9.36E−5), chronic obstructive pulmonary disease (COPD) (OR = 1.31, 95% CI = 1.16–1.49, p = 2.45E−5), lung cancer (OR = 1.18, 95% CI = 1.05–1.32, p = 0.005), and obstructive sleep apnea (OR = 1.12, 95% CI = 1.04–1.22, p = 0.003). MVPA was correlated with a reduced risk of developing asthma (OR = 0.68, 95% CI = 0.53–0.88, p = 0.004) and COPD (OR = 0.62, 95% CI = 0.47–0.83, p = 0.001). A genetic predisposition to SBW was associated with a decreased risk of nasal polyps (OR = 0.60, 95% CI = 0.423–0.86, p = 0.005). Conclusion: Our findings demonstrate complex causal relationships among sedentary lifestyle, physical activity, and various respiratory system diseases. These discoveries hold significant value in devising precision-oriented approaches for the prevention and treatment of respiratory diseases.