Causal associations of obstructive sleep apnea with cardiovascular disease: A Mendelian randomization study


 
 
 Obstructive sleep apnea (OSA) had been associated with various cardiovascular diseases (CVDs) in observational studies, but causal inferences have not been confirmed. We used the Mendelian randomization study to explore the potential causal association between OSA with CVDs in the general population.
 
 
 
 We performed a two-sample Mendelian randomization analysis using five gene-wide significant ﻿single-nucleotide polymorphisms (SNPs) associated with OSA at genome-wide significance from the FinnGen study (N=217955) and 12 cardiovascular diseases from the UK Biobank and the genetic consortia. The inverse-variance weighted (IVW) was chosen as the primary analysis and was complemented by various sensitivity analyses. The study design applied univariable MR, multivariable MR, and mediation analysis.
 
 
 
 MR analyses provide evidence of genetically predicted OSA on the risk of heart failure (﻿odds ratio (OR),1.26; 95% confidence interval (CI),1.08-1.47), hypertension (OR,1.24; 95%CI, 1.11-1.39) and atrial fibrillation (OR,1.21; 95%CI,1.12-1.31). Multivariable MR indicated the adverse effect of OSA on heart failure persisted after adjusting BMI, smoking, drinking and education (IVW OR,1.13; 95%CI, 1.01-1.27). However, the significance of hypertension and atrial fibrillation was dampened. Mediation analyses suggest that the causal association between OSA and heart failure is mediated in part by Apolipoprotein B, with a mediated portion of 9%.
 
 
 
 This study suggested that genetically predicted OSA is a potential causal risk factor for heart failure based on large-scale population. Nevertheless, further studies regarding ancestral diversity are needed to confirm the causal association between OSA and CVDs.
