Causal Relationship Between Childhood Obesity and Sleep Apnea Syndrome: Bidirectional Two-Sample Mendelian Randomization Analysis

Ping Wang,&ast; Shuli Liu,&ast; Ling Min Kong, Nannan Qi Department of Pediatrics, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, 271000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nannan Qi, Department of Pediatrics, The Second Affiliated Hospital of Shandong First Medical University, No. 366, Taishan Street, Taian, Shandong, 271000, People’s Republic of China, Email [email protected]: Childhood obesity has become a global pandemic, leading to a range of diseases. Childhood obesity appears to be associated with an increased prevalence of sleep apnea syndrome. Sleep apnea is an inestimable risk factor for thrombosis, hypertension, cardiomyopathy and many other diseases. Therefore, exploring the relationship between childhood obesity and sleep apnea syndrome will help to understand the potential link between the two and provide research directions for future disease prevention and treatment. However, no studies have confirmed whether there is a causal relationship between childhood obesity and sleep apnea syndrome.Methods: The IEU OpenGWAS project provided the GWAS-aggregated data for childhood obesity and sleep apnea syndrome. Inverse-variance weighted (IVW) was used as the main method to evaluate the causal relationship between childhood obesity and sleep apnea syndrome. Single nucleotide polymorphisms (SNPs) were regarded as instrumental variables, and the screening threshold was P < 5.0× 10− 6. Leave-one-out method was performed to confirm the robustness of the results.Results: IVW analysis confirmed a causal relationship between genetic susceptibility to childhood obesity and an increased risk of sleep apnea syndrome [odds ratio (OR)=1.12, 95% confidence interval (CI): 1.02– 1.23, P=0.016]. However, two-sample MR results also showed no causal relationship between genetic susceptibility to sleep apnea syndrome and an increased risk of childhood obesity (OR=1.50, 95% CI: 0.95– 2.38, P=0.083). The intercept of MR-Egger regression was close to 0, which implies that there are no confounding factors in the analysis to affect the results of two-sample MR analysis. The leave-one-out results show that the bidirectional two-sample MR analysis results were robust.Conclusion: There is a causal relationship between genetic susceptibility to childhood obesity and increased risk of sleep apnea syndrome. People with a history of childhood obesity should pay more attention to physical examination to early prevention and management of sleep apnea syndrome.Keywords: bidirectional two-sample Mendelian randomization, childhood obesity, sleep apnea syndrome, causal relationship, single nucleotide polymorphisms