Hou Yawei, Li Yameng, Xiao Zhenwei, Wang Zhenguo
Institute of Chinese Medical Literature and Culture, Shandong University of Traditional Chinese Medicine, Jinan, China.
The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China.
Front Neurol. 2024 Sep 4;15:1323928. doi: 10.3389/fneur.2024.1323928. eCollection 2024.
Observational studies have suggested an association between obstructive sleep apnea (OSA), chronic kidney disease (CKD), and renal function, and vice versa. However, the results from these studies are inconsistent. It remains unclear whether there are causal relationships and in which direction they might exist.
We used a two-sample Mendelian randomization (MR) method to investigate the bidirectional causal relation between OSA and 7 renal function phenotypes [creatinine-based estimated glomerular filtration rate (eGFRcrea), cystatin C-based estimated glomerular filtration rate (eGFRcys), blood urea nitrogen (BUN), rapid progress to CKD, rapid decline of eGFR, urinary albumin to creatinine ratio (UACR) and CKD]. The genome-wide association study (GWAS) summary statistics of OSA were retrieved from FinnGen Consortium. The CKDGen consortium and UK Biobank provided GWAS summary data for renal function phenotypes. Participants in the GWAS were predominantly of European ancestry. Five MR methods, including inverse variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode were used to investigate the causal relationship. The IVW result was considered the primary outcome. Then, Cochran's Q test and MR-Egger were used to detect heterogeneity and pleiotropy. The leave-one-out analysis was used for testing the stability of MR results. RadialMR was used to identify outliers. Bonferroni correction was applied to test the strength of the causal relationships ( < 3.571 × 10).
We failed to find any significant causal effect of OSA on renal function phenotypes. Conversely, when we examined the effects of renal function phenotypes on OSA, after removing outliers, we found a significant association between BUN and OSA using IVW method (OR: 2.079, 95% CI: 1.516-2.853; = 5.72 × 10).
This MR study found no causal effect of OSA on renal function in Europeans. However, genetically predicted increased BUN is associated with OSA development. These findings indicate that the relationship between OSA and renal function remains elusive and requires further investigation.
观察性研究表明阻塞性睡眠呼吸暂停（OSA）、慢性肾脏病（CKD）和肾功能之间存在关联，反之亦然。然而，这些研究的结果并不一致。目前尚不清楚它们之间是否存在因果关系以及因果关系的方向。
我们采用两样本孟德尔随机化（MR）方法来研究OSA与7种肾功能表型[基于肌酐的估计肾小球滤过率（eGFRcrea）、基于胱抑素C的估计肾小球滤过率（eGFRcys）、血尿素氮（BUN）、快速进展至CKD、eGFR快速下降、尿白蛋白与肌酐比值（UACR）和CKD]之间的双向因果关系。OSA的全基因组关联研究（GWAS）汇总统计数据来自芬兰基因组联盟。CKDGen联盟和英国生物银行提供了肾功能表型的GWAS汇总数据。GWAS的参与者主要为欧洲血统。使用了五种MR方法，包括逆方差加权（IVW）、MR-Egger、简单模式、加权中位数和加权模式来研究因果关系。IVW结果被视为主要结果。然后，使用 Cochr an's Q检验和MR-Egger来检测异质性和多效性。留一法分析用于检验MR结果的稳定性。使用RadialMR识别异常值。应用Bonferroni校正来检验因果关系的强度（<3.571×10）。
我们未发现OSA对肾功能表型有任何显著因果效应。相反，当我们研究肾功能表型对OSA的影响时，在去除异常值后，我们使用IVW方法发现BUN与OSA之间存在显著关联（OR：2.079，95%CI：1.516-2.853；=5.72×10）。
这项MR研究未发现OSA对欧洲人肾功能有因果效应。然而，基因预测的BUN升高与OSA的发生有关。这些发现表明OSA与肾功能之间的关系仍然难以捉摸，需要进一步研究。
