Abstract
BackgroundObservational studies have suggested that obstructive sleep apnea (OSA) is in relation to atrial fibrillation (AF); however, these studies might be confounded and whether the relationship is causal remains unclear. We conducted a bidirectional Mendelian randomization (MR) study to clarify the causal inference between OSA and AF.MethodsGenetic instruments for OSA and AF were obtained from genome-wide association studies. The fixed-effects inverse-variance weighted (IVW) method was used as the main method, supplemented by several sensitivity analyses. For replication, another AF dataset was used to validate the causal effect of OSA on AF. Furthermore, multivariable MR analyses were performed to obtain direct estimates adjusting for potential confounders.ResultsGenetic liability to OSA was found to be significantly associated with a higher AF risk in the fixed-effects IVW method [odds ratio (OR) 1.210; 95% CI 1.119–1.307; P = 1.51 × 10–6]. The results were consistent in MR sensitivity analyses as well as in replication analyses, and the significance remained after adjusting for potential confounders. In the reverse MR analyses, there was no causal effect of AF on OSA.ConclusionsOur study strengthened the causal evidence of genetically predicted OSA with a higher AF risk. Early screening and appropriate management of OSA might show anti-arrhythmic benefits.
Highlights
Observational studies have suggested that obstructive sleep apnea (OSA) is in relation to atrial fibrillation (AF); these studies might be confounded and whether the relationship is causal remains unclear
Mendelian randomization (MR) approach builds upon three important assumptions: (1) the instrumental variables (IVs) are strongly associated with the exposure, (2) the IVs are independent of any confounders, and (3) the IVs affect the outcome only through the exposure but not via other pathways (Fig. 1)
Genetic liability to OSA with AF In the fixed-effects inverse-variance weighted (IVW) analysis, genetic liability to OSA was associated with a higher risk of AF using the outcome dataset from Nielsen et al (Fig. 2, Additional file 1: Table S5)
Summary
Observational studies have suggested that obstructive sleep apnea (OSA) is in relation to atrial fibrillation (AF); these studies might be confounded and whether the relationship is causal remains unclear. Due to an aging population and increased prevalence of risk factors, AF is associated with high morbidity and mortality, and increasingly contributes to a significant burden to patients, physicians, and healthcare systems globally [2]. The prevalence of OSA was higher in patients with AF compared with the general population [4]; the prevalence of AF in patients with sleep apnea was much higher than control participants [5]. OSA and AF share many risk factors and comorbidities, such as increasing age, male gender, obesity, hypertension, heart failure, and coronary
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
