State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Ann Am Thorac Soc. 2022 Nov;19(11):1913-1919. doi: 10.1513/AnnalsATS.202112-1331OC.
Growing evidence has suggested that body water content plays a critical role in sleep apnea. However, the causal relationship has not been established. This study aimed to investigate whether increased whole-body water mass is causally associated with a higher risk of sleep apnea using two-sample Mendelian randomization (MR) analysis. Body water mass (BWM)-associated genetic instruments were extracted from a genome-wide association study conducted by Neale Lab, which incorporates 331,315 individuals of European ancestry. Genetic variants for sleep apnea were derived from the FinnGen dataset. MR analysis was performed using inverse variance-weighted and weight median methods, respectively. MR-Egger regression and MR-Pleiotropy Residual Sum and Outlier tests were applied to evaluate the directional pleiotropy. In addition, we performed a multivariable MR analysis that includes body mass index, snoring, and waist-to-hip ratio as covariate exposures to address their confounding effects. To elucidate mechanisms of the association between BWM and sleep apnea, we further conducted MR analysis on common edematous diseases. MR estimates showed that per standard deviation increase in BWM led to an increase in the risk of sleep apnea by 49% (odds ratio [OR], 1.490; 95% confidence interval [CI], 1.308-1.696; = 1.75 × 10). The result after MR-Pleiotropy Residual Sum and Outlier correction further supports their causal association (OR, 1.414; 95% CI, 1.253-1.595; = 1.76 × 10). In addition, the multivariable MR analysis indicates a significant causal association between a higher BWM and increased risk of sleep apnea (OR, 1.204; 95% CI, 1.031-1.377; = 0.036). Genetic predisposition to a higher BWM was also causally related to increased risk of edematous diseases. Our results suggested that increased BWM is a potential risk factor for sleep apnea. Pathologic edema is a possible intermediate factor mediating this causal association.
越来越多的证据表明，体水含量在睡眠呼吸暂停中起着关键作用。然而，因果关系尚未建立。本研究旨在使用两样本 Mendelian 随机化 (MR) 分析来研究全身水质量增加是否与睡眠呼吸暂停的更高风险有因果关系。体水质量 (BWM) 相关的遗传工具是从 Neale 实验室进行的全基因组关联研究中提取的，该研究纳入了 331315 名欧洲血统个体。睡眠呼吸暂停的遗传变异来自 FinnGen 数据集。MR 分析分别使用逆方差加权和加权中位数方法进行。MR-Egger 回归和 MR-Pleiotropy Residual Sum and Outlier 检验用于评估定向 pleiotropy。此外，我们进行了多变量 MR 分析，其中包括体重指数、打鼾和腰臀比作为协变量暴露，以解决它们的混杂影响。为了阐明 BWM 与睡眠呼吸暂停之间关联的机制，我们还对常见的水肿性疾病进行了 MR 分析。MR 估计表明，BWM 每增加一个标准差，睡眠呼吸暂停的风险就会增加 49%（优势比 [OR]，1.490；95%置信区间 [CI]，1.308-1.696； = 1.75 × 10）。MR-Pleiotropy Residual Sum and Outlier 校正后的结果进一步支持了它们的因果关联（OR，1.414；95% CI，1.253-1.595； = 1.76 × 10）。此外，多变量 MR 分析表明，BWM 较高与睡眠呼吸暂停风险增加之间存在显著的因果关系（OR，1.204；95% CI，1.031-1.377； = 0.036）。更高的 BWM 遗传易感性也与水肿性疾病风险增加有因果关系。我们的结果表明，BWM 增加是睡眠呼吸暂停的一个潜在危险因素。病理性水肿可能是介导这种因果关系的中间因素。
