BackgroundObstructive sleep apnea (OSA) has shown to be associated with an increased risk of atrial fibrillation in observational studies. Whether this association reflect causal effect is still unclear. The aim of this study was to evaluate the causal effect of OSA on atrial fibrillation.Methods and ResultsWe used a 2‐sample Mendelian randomization (MR) method to evaluate the causal effect of OSA on atrial fibrillation. Summary data on genetic variant‐OSA association were obtained from a recently published genome‐wide association studies with up to 217 955 individuals and data on variant‐atrial fibrillation association from another genome‐wide association study with up to 1 030 836 individuals. Effect estimates were evaluated using inverse‐variance weighted method. Other MR analyses, including penalized inverse‐variance weighted, penalized robust inverse‐variance weighted, MR‐Egger, simple median, weighted median, weighted mode‐based estimate and Mendelian Randomization Pleiotropy Residual Sum and Outlier methods were performed in sensitivity analyses. The MR analyses in both the fixed‐effect and random‐effect inverse‐variance weighted models showed that genetically predicted OSA was associated with an increased risk of atrial fibrillation (odds ratio [OR], 1.21; 95% CI, 1.12–1.31, P<0.001; OR, 1.21; 95% CI, 1.11–1.32, P<0.001) using 5 single nucleotide polymorphisms as the instruments. MR‐Egger indicated no evidence of genetic pleiotropy (intercept, −0.014; 95% CI, −0.033 to 0.005, P=0.14). Results were robust using other MR methods in sensitivity analyses.ConclusionsThis MR analysis found that genetically predicted OSA had causal effect on an increased risk of atrial fibrillation.

中文翻译：

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阻塞性睡眠呼吸暂停对心房颤动的因果影响：孟德尔随机研究

背景在观察性研究中显示阻塞性睡眠呼吸暂停 (OSA) 与心房颤动风险增加有关。这种关联是否反映了因果关系尚不清楚。本研究的目的是评估 OSA 对心房颤动的因果影响。方法和结果我们使用 2 样本孟德尔随机 (MR) 方法来评估 OSA 对心房颤动的因果影响。遗传变异-OSA 关联的汇总数据来自最近发表的一项涉及多达 217 955 名个体的全基因组关联研究，以及来自另一项多达 1 030 836 名个体的全基因组关联研究的变异心房颤动关联数据。使用反方差加权方法评估效果估计。其他 MR 分析，包括惩罚性逆方差加权，在敏感性分析中进行了惩罚稳健逆方差加权、MR-Egger、简单中值、加权中值、基于加权模式的估计和孟德尔随机化多效性残差和和异常值方法。固定效应和随机效应逆方差加权模型中的 MR 分析表明，遗传预测的 OSA 与心房颤动风险增加相关（优势比 [OR]，1.21；95% CI，1.12-1.31，P <0.001；或，1.21；95% CI, 1.11–1.32, P <0.001) 使用 5 个单核苷酸多态性作为工具。MR-Egger 表明没有遗传多效性的证据（截距，-0.014；95% CI，-0.033 至 0.005，P = 0.14）。在敏感性分析中使用其他 MR 方法的结果是稳健的。结论该 MR 分析发现，基因预测的 OSA 对心房颤动风险增加具有因果影响。