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ORIGINAL RESEARCH article
Front. Neurol.
Sec. Sleep Disorders
Volume 15 - 2024 |
doi: 10.3389/fneur.2024.1323928
This article is part of the Research Topic Novel Technologies in the Diagnosis and Management of Sleep-Disordered Breathing: Volume II View all 13 articles
Causal Effects of Obstructive Sleep Apnoea on Chronic Kidney Disease and Renal Function: A Bidirectional Mendelian Randomization Study
Provisionally accepted- 1 Institute of Chinese Medical Literature and Culture, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
- 2 Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
- 3 Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
Background: Observational studies have suggested an association between obstructive sleep apnoea (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. Methods: We used a 2-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 (P < 3.571×10 -3 ). Results: 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; P = 5.72×10 -6 ). Conclusions: 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.
Keywords: obstructive sleep apnea, Chronic Kidney Disease, Renal function, Mendelian randomization, causal relationship
Received: 24 Nov 2023; Accepted: 23 Aug 2024.
Copyright: © 2024 Hou, Li, Xiao and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zhenguo Wang, Institute of Chinese Medical Literature and Culture, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
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