Impact of Chronic Kidney Disease on the Risk of Hearing Loss: A Retrospective Cohort Study and Genetic Analysis.

BACKGROUND: Hearing loss (HL) and chronic kidney disease (CKD) are both significant components of the global health burden. We explored the phenotypic association between CKD and HL, along with the underlying genetic drivers, through studies ranging from clinical cohorts to genetic analyses. METHODS: First, we utilized data from the China Health and Retirement Longitudinal Study (CHARLS) and assessed the relationship between CKD and hearing loss using Cox proportional hazards models. Subsequently, we employed genome-wide genetic aggregation data to investigate the genetic drivers underlying CKD and HL. RESULTS: In the cohort study, 7,084 individuals were included, of whom 1,509 participants (21.3%) experienced hearing loss. Cox regression analysis showed that CKD was associated with an increased risk of hearing loss (HR=1.541, 95% CI=1.317-1.804). In genetic analysis, CKD was positively genetically correlated with HL (rg=0.155, P<0.05). Multi-trait analysis of GWAS (MTAG) and cross-phenotype association analysis (CPASSOC) from the genome-wide association study identified two significant pleiotropic SNPs (rs12149832 and rs2044993) for both CKD and HL. Transcriptome-wide association study (TWAS) identified shared tissue-specific expression-trait associations, but Mendelian randomization did not reveal causal relationships (OR=1.035, 95% CI=0.973-1.101). CONCLUSIONS: Our cohort study confirms the clinical association between CKD and HL. Genetic analysis reveals a shared genetic link between the two conditions and potential underlying genetic drivers. These findings may provide effective strategies for preventing and managing hearing loss in clinical CKD patients.