Association of modifiable risk factors with obstructive sleep apnea: a Mendelian randomization study

Background: The risk factors involved in obstructive sleep apnea (OSA) have not been clearly identified yet. We attempted to systematically investigate genetically predicted modifiable risk factors and lifestyle behaviors associated with OSA.Methods: The association between 34 risk factors and OSA was evaluated using the two-sample Mendelian randomization (MR). Genetic variants for risk factors were acquired from European-descent genome-wide studies. Data sources for OSA were extracted from FinnGen study with 16,761 cases and 201,194 controls. The primary analysis chosen was the inverse-variance weighted method.Results: MR analyses provide evidence of genetically predicted poor overall health rating (odds ratio (OR), 2.82; 95% confidence interval (CI), 1.95-4.08), nap during day (OR, 2.01; 95% CI, 1.37-2.93), high body mass index (BMI) (OR, 1.14; 95% CI, 1.09-1.19), increased body fat mass (OR, 1.83; 95% CI, 1.83-2.05), elevated body water mass (OR, 1.50; 95% CI, 1.31-1.70) and hypertension (OR, 1.81; 95% CI, 1.34-2.45) were associated with higher OSA risk, while high education level (OR, 0.55; 95% CI, 0.40-0.75) correlated with reduced OSA risk. Suggestive evidence was obtained for smoking and waist-to-hip ratio (WHR) with higher OSA odds, and vigorous physical activity, and HDL cholesterol with lower OSA odds. After adjusting for BMI using multivariable MR analysis, the effects of smoking, WHR, vigorous physical activity, and HDL-cholesterol were fully attenuated. Conclusions: This MR study indicates that overall health rating, nap during day, BMI, body fat mass, body water mass, hypertension, and education are causally associated with the risk of OSA, which means that these modifiable risk factors are key targets for OSA prevention.