Mendelian randomization reveals the causal association between gout and hearing impairment in older adults

Abstract

With the global aging trend escalating, the holistic well-being of the elderly has become a paramount concern within public health. Traditional observational studies often struggle with confounding factors and establishing causality, leaving the relationship between age-related hearing loss (ARHL) and gout largely unexplored. Employing bidirectional two-sample Mendelian randomization (MR) analysis, this investigation elucidated the genetic underpinnings associated with age-related hearing impairment, gout, and urate levels within the IEU Open-GWAS database, thereby uncovering potential causal connections that underlie the intricate interplay between gout, serum urate concentrations, and auditory decline in the geriatric demographic. In the forward MR phase, a cohort of 30 single nucleotide polymorphisms was leveraged to dissect the causal dynamics between ARHL and both gout and urate concentrations. Conversely, in the reverse MR phase, gout and urate levels were posited as the exposome to delineate their impact on hearing acuity, employing an array of models for rigorous validation and sensitivity scrutiny. In the forward MR analysis, a statistically significant correlation was discerned between ARHL and gout (P = .003, odds ratio = 1.01, 95% confidence interval: 1.00–1.02), alongside a notable association with serum urate levels (P = .031, odds ratio = 1.39, 95% confidence interval: 1.03–1.88), intimating that ARHL could potentially influence the incidence of gout and urate concentrations. Conversely, the reverse MR investigation revealed that neither gout nor serum urate levels exerted significant impact on auditory degradation (P > .05), insinuating that these factors might not predominantly contribute to hearing loss. Sensitivity analyses concurred with this inference. This study enriches the comprehension of geriatric health intricacies and unveils that ARHL potentially influences gout and serum urate concentrations. This suggests that monitoring ARHL may play a crucial role in the early identification and management of gout and hyperuricemia, potentially contributing to a comprehensive approach to improving geriatric health outcomes.