Chen Gui, Gong Xin, Liu Shenrong, Xie Junyang, Wang Yingqi, Guo Wucheng, Liao Wenjing, Song Lijuan, Zhang Xiaowen
State Key Laboratory of Respiratory Disease, Department of Otolaryngology - Head and Neck Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
These authors contributed equally.
ERJ Open Res. 2023 Aug 29;9(4). doi: 10.1183/23120541.00127-2023. eCollection 2023 Jul.
Based on evidence from existing observational research, clarifying the causal relationship between gastro-oesophageal reflux disease (GORD) and obstructive sleep apnoea (OSA) is challenging. Here, Mendelian randomisation, a method based on genetics, was used to provide new evidence for causality.
Summary statistics from two publicly available genome-wide association studies were used to evaluate the causal relationship between GORD and OSA (the GORD database was used as an exposure variable and the OSA database as an outcome). Inverse variance weighting was used as the main analytical tool in Mendelian randomisation to estimate causal effects. The robustness of the results was evaluated by sensitivity analysis. Possible mediators were evaluated using multivariate Mendelian randomisation.
A statistically significant causal relationship was observed between GORD and OSA (OR 1.597, 95% CI 1.401-1.821, p<0.001), and similar results were observed in weighted median and Mendelian randomisation-Egger regression analyses. No bias was found in the sensitivity analysis of Mendelian randomisation estimation. Multivariate Mendelian randomisation showed that GORD significantly increased the risk of developing OSA, even when the possible mediator was excluded (OR 1.107, 95% CI 1.101-1.212, p<0.001).
Our study confirmed a causal relationship between GORD and OSA and suggests that intervention measures should be taken for patients with GORD to prevent the occurrence of OSA.
基于现有观察性研究的证据，阐明胃食管反流病（GORD）与阻塞性睡眠呼吸暂停（OSA）之间的因果关系具有挑战性。在此，孟德尔随机化这一基于遗传学的方法被用于提供因果关系的新证据。
使用两项公开可用的全基因组关联研究的汇总统计数据来评估GORD与OSA之间的因果关系（将GORD数据库用作暴露变量，OSA数据库用作结果）。逆方差加权法被用作孟德尔随机化中的主要分析工具来估计因果效应。通过敏感性分析评估结果的稳健性。使用多变量孟德尔随机化评估可能的中介因素。
观察到GORD与OSA之间存在统计学上显著的因果关系（比值比1.597，95%置信区间1.401 - 1.821，p<0.001），并且在加权中位数和孟德尔随机化 - 伊格回归分析中观察到类似结果。在孟德尔随机化估计的敏感性分析中未发现偏差。多变量孟德尔随机化表明，即使排除可能的中介因素，GORD仍显著增加发生OSA的风险（比值比1.107，95%置信区间1.101 - 1.212，p<0.001）。
我们的研究证实了GORD与OSA之间的因果关系，并建议应对GORD患者采取干预措施以预防OSA的发生。
