ABSTRACT

Background:
Previous observational studies have reported the association between obstructive sleep apnea (OSA) and diabetic nephropathy. However, it remains to be confirmed whether this association is causal. This study aimed to investigate the causal association of OSA with diabetic nephropathy and the mediating effect of common risk factors using Mendelian randomization (MR) design.

Method:
The study data were sourced from genome-wide association studies (GWAS). Bidirectional two-sample MR and multivariable MR analyses were conducted to assess causal relationships between OSA and diabetic nephropathy. Potential mediation by common risk factors was evaluated through two-step MR. In addition, the MR results were supported by various sensitivity and validation analyses.

Results:
We presented genetic evidence that OSA could unidirectionally increase the risk of diabetic nephropathy (OR = 1.30; 95 % CI: 1.13, 1.50; p = 2.51 × 10-4). After adjusting for BMI, high blood pressure, blood glucose levels, glycated hemoglobin levels, severe insulin resistance, years of schooling, nap during day, processed meat consumption, and coffee intake, the causal effect of OSA on diabetic nephropathy remained statistically significant. Further mediation MR analysis showed that BMI and high blood pressure may mediate the causal relationship between OSA and diabetic nephropathy, with a mediation effect of 26.35 % and 9.91 %, respectively.

Conclusion:
Our findings suggest that genetically predicted OSA is associated with a higher risk of diabetic nephropathy. Additionally, BMI and high blood pressure are involved in the mechanism of OSA-induced diabetic nephropathy.

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