Genetic association between renal function and hearing loss: a bidirectional Mendelian randomization study

OBJECTIVE: Evidence from observational epidemiology studies suggested that renal dysfunction was associated with hearing loss. Whether this represents a causal, reverse causal or correlative relationship remains unclear. We investigated this using a bidirectional two-sample Mendelian Randomization (MR) approach. METHODS: We retrieved genetic variants associated with renal function biomarkers, including creatinine-based eGFR (eGFR-crea), cystatin C-based eGFR (eGFR-cys), urine albumin-to-creatinine ratio (UACR), and serum urate, from the CKDGen Consortium. The summary-level datasets of hearing loss were retrieved from the GWAS of UK Biobank. Inverse-Variance Weighted (IVW) method was the main analysis. RESULTS: The MR analysis revealed a significant association between genetically predicted UACR and the risk of hearing loss (IVW: OR = 1.038, 95% CI 1.002-1.074, p = 0.036). However, we did not find evidence for a causal effect of eGFR-crea (IVW: OR = 1.046, 95% CI 0.953-1.149, p = 0.342), eGFR-cys (IVW: OR = 0.997, 95% CI 0.940-1.058, p = 0.932) and urate (IVW: OR = 0.999, 95% CI 0.990-1.009, p = 0.904) on hearing loss. Moreover, we found no evidence that hearing loss had causal effects on renal function in the reverse MR analyses. Sensitivity analyses also confirmed the robustness of these findings. CONCLUSION: This study provides genetic evidence that elevated UACR is a potential risk factor for hearing loss, but does not support a causal role of hearing loss on kidney function. LEVEL OF EVIDENCE: Level 2.