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. 2022 Feb 11:9:843681.
doi: 10.3389/fcvm.2022.843681. eCollection 2022.

Assessment of the Causal Effects of Obstructive Sleep Apnea on Atrial Fibrillation: A Mendelian Randomization Study

Yalan Li  1   2 , Yiming Leng  1   2 , Haibo Tang  3 , Peizhi Deng  1   2 , Jie Wang  1   2 , Hong Yuan  1   2 , Rujia Miao  1 , Ping Mu  4
Affiliations

Assessment of the Causal Effects of Obstructive Sleep Apnea on Atrial Fibrillation: A Mendelian Randomization Study

Yalan Li et al. Front Cardiovasc Med. .

Abstract

Background: Obstructive sleep apnea (OSA) and atrial fibrillation (AF) are epidemiologically correlated, but the causal relationship between them remains elusive. We aimed to explore the causal relationships between OSA and AF.

Method: Using both the Finnish biobank and publicly available genome-wide association study data (GWAS), we conducted a two-sample Mendelian randomization (MR) analysis to estimate the causal effect of OSA on AF, both in the primary analysis and replicated analysis. The inverse variance weighted MR was selected as the main method. To further test the independent causal effect of OSA on AF, we also performed multivariable MR (MVMR), adjusting for body mass index (BMI), hypertension, and coronary artery disease (CAD), respectively.

Results: In the primary analysis, OSA was significantly associated with the increased risk of AF (OR 1.21, 95% CI 1.11-1.32) and the replicated analysis showed consistent results (OR 1.17, 95% CI 1.05-1.30). Besides, there was no heterogeneity and horizontal pleiotropy observed both in the primary and replicated analysis. Further multivariable MR suggested that the causal relationships between OSA and AF exist independently of BMI and CAD. The MVMR result after the adjustment for hypertension is similar in magnitude and direction to the univariable MR. But it did not support a causal relationship between OSA and AF.

Conclusion: Our study found that genetically driven OSA causally promotes AF. This causal relationship sheds new light on taking effective measures to prevent and treat OSA to reduce the risk of AF.

Keywords: Mendelian randomization; atrial fibrillation; causal inference; instrumental variable (IV); obstructive sleep apnea.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Diagram of Mendelian randomization (MR) framework in this study. SNP, single nucleotide polymorphisms; OSA, obstructive sleep apnea; AF, atrial fibrillation; GWAS, genome-wide association study; MR, mendelian randomization; BMI, body mass index; HTN, hypertension; CAD, coronary artery disease.
Figure 2
Figure 2
Scatter plot [primary analysis, (A); replicated analysis, (B)] and leave-one-out test [primary analysis, (C); replicated analysis, (D)] for genetically determined obstructive sleep apnea (OSA) on atrial firbrillation (AF) risk. SNP, single nucleotide polymorphisms; OSA, obstructive sleep apnea; AF, atrial fibrillation; MR, mendelian randomization.
Figure 3
Figure 3
The association between genetically determined OSA and the AF risk using univariable and multivariable inverse-variance weighted (IVW) MR adjusted for body mass index (BMI), hypertension (HTN), and coronary artery disease (CAD). UVMR, univariable mendelian randomization; MVMR, multivariable mendelian randomization; SNP, single-nucleotide polymorphism; OR, odds ratio; CI, confidence interval; BMI, body mass index; HTN, hypertension; CAD, coronary artery disease; IVW, inverse-variance weighted; OSA, obstructive sleep apnea; AF, atrial fibrillation.
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