A two-sample Mendelian randomization study on physical activity and sensorineural hearing loss

LI Peng; FAN Fengxia; ZHONG Lei; XIAO Mingxing; PENG Xuemei; LÜ Huaiqing; CHEN Zhipeng

doi:10.3969/j.issn.1672-2922.2026.01.009

Abstract：Objective Sensorineural hearing loss(SNHL)is a common auditory disorder worldwide and may be associated with multiple factors.Recent studies suggest that physical activity(PA)may have a protective effect against SNHL,but the causal relationship remains unclear.This study employs Mendelian randomization(MR)analysis to investigate the potential causal relationship between PA and SNHL.Methods A two-sample MR analysis was conducted based on summary statistics from published genome-wide association studies(GWAS).Data were obtained from the publicly available MRC IEU GWAS database.Single nucleotide polymorphisms(SNPs)significantly associated with PA and SNHL were selected as instrumental variables.Two PA phenotypes were included in the analysis:the number of days per week engaging in at least 10 minutes of moderate-intensity physical activity(MPA 10+min)(GWAS ID:ukb-a-508,sample size=321 309)and the number of days per week engaging in at least 10 minutes of vigorous-intensity physical activity(VPA 10+min)(GWAS ID:ukb-b-151,sample size=440 512).To avoid sample overlap between exposure and outcome groups,SNHL data were obtained from the FinnGen consortium(finn-b-H8_HL_SEN_NAS),comprising 15 952 cases and 196 592 controls.MR analyses were performed using the inverse-variance weighted(IVW)method,MR-Egger regression,and the weighted median(WM)approach.Horizontal pleiotropy was assessed using MR-Egger regression and MR-PRESSO,while heterogeneity was evaluated using Cochran's Q test.Additionally,leave-one-out sensitivity analysis was conducted to ensure the robustness and reliability of the results.Results The IVW analysis demonstrated a negative association between PA and the relative risk of SNHL("MPA 10+min":IVW:OR=0.689,P=0.013,95%CI=0.514～0.924;"VPA 10+min":OR=0.625,P=0.001,95%CI=0.468～0.835).The WM method yielded results consistent with those of the IVW method.Sensitivity analyses indicated no evidence of heterogeneity or horizontal pleiotropy.The leave-one-out analysis confirmed that the findings were robust and not influenced by any individual instrumental variable.Conclusions This MR study provides causal evidence suggesting that PA may reduce the risk of SNHL.These findings support the potential role of PA in hearing protection.However,further research is needed to validate these results and explore underlying biological mechanisms.