Bidirectional two-sample Mendelian randomization analysis identifies causal associations between kidney function and Sleep apnea

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Bidirectional two-sample Mendelian randomization analysis identifies causal associations between kidney function and Sleep apnea

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Co-author 1

Sihua Xu xush83@mail2.sysu.edu.cn Sun Hat-sen University School of Public Health (Shenzhen) Shenzhen China *

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Introduction

Sleep apnea (SA), characterized by recurrent apnea and hypopnea during sleep, includes central and obstructive subtypes. The comorbidity of chronic kidney disease (CKD) and sleep apnea is highly prevalent in clinical practice. While observational studies suggest an association between SA and kidney dysfunction, the causal relationship and underlying mechanisms remain unclear. This study conducted a bidirectional Mendelian randomization (MR) analysis to investigate bidirectional causal effects between SA and kidney function indicators.

Methods

We performed bidirectional univariate MR analyses using genetic instruments. The data of individuals with SA data (21,232 cases/604,917 controls) were obtained from UK Biobank and FinnGen consortium. Genome-wide association study summary statistics for kidney function biomarkers were obtained from the Chronic Kidney Disease Genetics Consortium, including blood urea nitrogen (BUN, N=852,678), creatinine-based estimated glomerular filtration rate (eGFRcrea, N=1,004,040), cystatin C-based eGFR (eGFRcys, N=460,826), urinary albumin-to-creatinine ratio (UACR, N=547,361), and serum urate (N=288,649). Inverse-variance weighted method was used as primary analysis with supplementary MR methods.

Results

The forward MR analysis demonstrated significant causal effects of kidney function on SA: eGFRcrea (OR=0.516, 95% CI: 0.358-0.744) and eGFRcys (OR=0.786, 95% CI: 0.647-0.955) showed protective effects, while BUN showed risk-increasing effect (OR=1.689, 95% CI: 1.269-2.248). The reverse MR analysis indicated SA significantly increased urate levels (OR=1.108, 95% CI: 1.037-1.184). No significant causal relationship was found between UACR and SA in either direction.

Conclusion

This MR study provides evidence for bidirectional causal relationships between sleep apnea and kidney function. Impaired glomerular filtration rate and elevated BUN appear to increase SA risk, while SA contributes to elevated urate levels. These findings suggest potential pathophysiological interactions between respiratory dysfunction during sleep and renal impairment that warrant further investigation.

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