PDF(Pubmed)
Abstract：
Background: In observational studies, gastroesophageal reflux disease (GERD) is linked to atrial fibrillation (AF). It is uncertain whether the relationship is due to GERD-induced AF or GERD caused by AF, or confusion with factors related to GERD and AF such as obesity and sleep-disordered breathing. We applied bidirectional Mendelian randomization (MR), in which genetic variations are used as instrumental variables to resolve confounding and reverse causation issues, to determine the causal effect between GERD and AF. Methods: Using summary data from the GERD and AF genome-wide association study (GWAS), a bidirectional MR was performed to estimate the causative impact of GERD on AF risk and AF on GERD risk. The GWAS of GERD meta-analysis comprised 78707 cases and 288734 controls. GWAS summary data for AF, including 45766 AF patients and 191924 controls, were used to genetically predicted AF. The inverse variance weighted (IVW) method was the major MR approach used. MR-PRESSO was implemented to detect heterogeneity and correct the effect of outliers. Weighted median and MR-Egger regression were applied to test heterogeneity and pleiotropy. Results: The genetic instruments of GERD related to increasing the risk of AF, with an OR of 1.339 (95% CI: 1.242-1.444, p < 0.001). However, after removing the outlier 8 SNPs, genetically predicted AF was not associated with an elevated risk of GERD (p = 0.351). Conclusions: Our result suggested that GERD had a causal effect on AF. However, no evidence was identified that AF elevated the risk of GERD.
摘要：
背景：在观察性研究中，胃食管反流病（GERD）与心房颤动（AF）有关。不确定这种关系是由于GERD诱发的房颤还是由房颤引起的GERD引起的,或与GERD和AF相关的因素如肥胖和睡眠呼吸障碍混淆。我们应用双向孟德尔随机化(MR)，其中遗传变异被用作工具变量来解决混杂和反向因果关系问题，以确定GERD和AF之间的因果关系。方法：使用GERD和AF全基因组关联研究(GWAS)的汇总数据，我们进行了双向MR评估GERD对AF风险和AF对GERD风险的致病影响.GERD的GWAS荟萃分析包括78707例和288734例对照。房颤的GWAS汇总数据，包括45766例房颤患者和191924年的对照，用于基因预测房颤。逆方差加权(IVW)方法是使用的主要MR方法。实施MR-PRESSO以检测异质性并校正异常值的影响。加权中位数和MR-Egger回归用于测试异质性和多效性。结果：GERD的遗传工具与房颤风险增加有关，OR为1.339（95%CI：1.242-1.444，p<0.001）。然而,在删除8个SNP的离群值之后，遗传预测的AF与GERD风险升高无关(p=0.351).结论：我们的结果表明GERD对AF有因果关系。然而,没有证据表明房颤会增加GERD的风险.
