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Obstructive sleep apnea and atrial fibrillation: insights from a bidirectional Mendelian randomization study
Lu Chen1, Xingang Sun1, Yuxian He1
1Department of Cardiology and Atrial Fibrillation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang Province, People's Republic of China.
Background:
Observational 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.
Methods:
Genetic 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.
Results:
Genetic 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.
Conclusions:
Our 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.
Insights
Obstructive sleep apnea (OSA) causally increases the risk of atrial fibrillation (AF). Treating OSA may help prevent AF, as AF does not appear to cause OSA.
Area of Science:
- Cardiology
- Genetics
- Sleep Medicine
Background:
- Observational studies suggest a link between obstructive sleep apnea (OSA) and atrial fibrillation (AF).
- Previous studies may be confounded, leaving the causal nature of the OSA-AF relationship unclear.
Purpose of the Study:
- To clarify the causal inference between obstructive sleep apnea (OSA) and atrial fibrillation (AF).
- To investigate the relationship using a bidirectional Mendelian randomization (MR) approach.
Main Methods:
- Utilized genetic instruments for OSA and AF from genome-wide association studies.
- Employed the fixed-effects inverse-variance weighted (IVW) method as the primary analysis.
- Conducted sensitivity analyses, replication analyses, and multivariable MR to confirm findings and adjust for confounders.
Main Results:
- Genetic liability to OSA was significantly associated with an increased risk of AF (OR 1.210, P=1.51×10⁻⁶).
- Findings were consistent across sensitivity, replication, and multivariable MR analyses.
- Reverse MR analyses indicated no causal effect of AF on OSA.
Conclusions:
- This study provides strong causal evidence linking genetically predicted OSA to a higher risk of AF.
- Early screening and effective management of OSA may offer anti-arrhythmic benefits, potentially reducing AF incidence.
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