Mendelian randomization reveals no associations of genetically-predicted obstructive sleep apnea with the risk of type 2 diabetes, nonalcoholic fatty liver disease, and coronary heart disease

BACKGROUND: Obstructive sleep apnea (OSA) has been reported to affect cardiometabolic diseases. However, whether such association is causal is still unknown. Here, we attempt to explore the effect of OSA on type 2 diabetes (T2D), nonalcoholic fatty liver disease (NAFLD) and coronary heart disease (CHD). METHODS: Genetic variants associated with OSA were requested from a published genome-wide association study (GWAS) and those qualified ones were selected as instrumental variables (IV). Then, the IV-outcome associations were acquired from T2D, NAFLD and CHD GWAS consortia separately. The Mendelian randomization (MR) was designed to estimate the associations of genetically-predicted OSA on T2D, NAFLD and CHD respectively, using the inverse-variance weighted (IVW) method. We applied the Bonferroni method to adjust the p-value. Besides, MR-Egger regression and weighted median methods were adopted as a supplement to IVW. The Cochran's Q value was used to evaluate heterogeneity and the MR-Egger intercept was utilized to assess horizontal pleiotropy, together with MR-PRESSO. The leave-one-out sensitivity analysis was carried out as well. RESULTS: No MR estimate reached the Bonferroni threshold (p < 0.017). Although the odds ratio of T2D was 3.58 (95% confidence interval (CI) [1.06, 12.11], IVW-p-value = 0.040) using 4 SNPs, such causal association turned insignificant after the removal of SNP rs9937053 located in FTO [OR = 1.30 [0.68, 2.50], IVW p = 0.432]. Besides, we did not find that the predisposition to OSA was associated with CHD [OR = 1.16 [0.70, 1.91], IVW p = 0.560] using 4 SNPs. CONCLUSION: This MR study reveals that genetic liability to OSA might not be associated with the risk of T2D after the removal of obesity-related instruments. Besides, no causal association was observed between NAFLD and CHD. Further studies should be carried out to verify our findings.