Polygenic risk score analysis of noise-induced hearing loss: An integrated cross-sectional and longitudinal study

Background: Substantial variability in susceptibility to noise-induced hearing loss (NIHL) with comparable noise exposures suggests a genetic contribution, but population-based evidence remains limited. This study evaluated whether a polygenic risk score (PRS), summarizing the effect of genetic variants, was associated with NIHL susceptibility. Methods: Participants were recruited from an ongoing Occupational Noise Exposure and Health Study (ONEHS), including 3836 NIHL cases and 2028 normal hearing (NH) controls. A weighted PRS, calculated from seven genetic variants, stratified participants into low (0–20%), moderate (20–80%), and high (80–100%) PRS groups. Cross-sectional associations with prevalence of NIHL were assessed using logistic regression, while longitudinal associations with incident NIHL and hearing deterioration were evaluated using Cox proportional hazards models and generalized estimating equations. Results: For cross-sectional analyses, participants with high PRS had an increased NIHL risk relative to low PRS participants (odds ratio [OR] = 1.35, 95% confidence interval [CI]: 1.13–1.63, P = 0.001). PRS exhibited an interaction with cumulative noise exposure (CNE). For the longitudinal study (907 with NH and 897 with mild hearing loss at baseline), approximately one–third of participants experienced hearing deterioration. High PRS participants showed increased risk of developing NIHL (hazard ratio [HR] = 1.57, 95% CI: 1.13–2.18, P = 0.008) and further hearing deterioration (HR = 1.49, 95% CI: 1.08–2.07, P = 0.017). Joint associations were observed for high PRS with CNE and age. Conclusions: Common genetic variation, captured by PRS, contributes to NIHL susceptibility and modifies the relationship between noise exposure and hearing outcomes.