Department 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.
BMC Med Genomics. 2022 Feb 16;15(1):28. doi: 10.1186/s12920-022-01180-5.
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.
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.
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]. 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.
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.
观察性研究表明阻塞性睡眠呼吸暂停（OSA）与心房颤动（AF）有关；然而，这些研究可能存在混杂因素，并且这种关系是否具有因果关系尚不清楚。我们进行了一项双向孟德尔随机化（MR）研究，以阐明 OSA 和 AF 之间的因果关系。
OSA 和 AF 的遗传工具来自全基因组关联研究。固定效应逆方差加权（IVW）方法被用作主要方法，并辅以几种敏感性分析。为了验证，使用另一个 AF 数据集来验证 OSA 对 AF 的因果效应。此外，进行了多变量 MR 分析，以获得调整潜在混杂因素的直接估计值。
固定效应 IVW 方法发现 OSA 的遗传易感性与更高的 AF 风险显著相关[比值比（OR）1.210；95%置信区间（CI）1.119-1.307；P=1.51×10]。敏感性分析和验证分析的结果一致，在调整潜在混杂因素后，该结果仍然显著。在反向 MR 分析中，AF 对 OSA 没有因果影响。
我们的研究加强了遗传预测的 OSA 与更高的 AF 风险之间的因果关系证据。早期筛查和适当管理 OSA 可能显示出抗心律失常的益处。
