A Mendelian randomization analysis of lipid metabolism and the risk of speech recognition difficulties under noise conditions

CAO Yang; WU Xiaonan; LI Danyang; WANG Hongyang; WANG Qiuju

doi:10.3969/j.issn.1672-2922.2026.01.005

Abstract：Objective To investigate the relationship between lipid metabolism markers and hearing difficulty in noise,as well as their roles in early stages of hearing loss.Methods Based on Mendelian randomization(MR)design,and using data from two large-scale genome-wide association study databases,i.e.the UK Biobank and the Global Lipids Genetic Consortium,associations between lipid metabolism indicators,such as high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),triglycerides,and speech recognition difficulties in noise were evaluated.The inverse-variance weighted method was employed as the primary analytical approach,and multivariable MR analysis was conducted to further validate the independent contribution of lipid metabolism markers.Results Two-sample MR analysis revealed a significant protective relationship between HDL-C and hearing difficulty in noise(UK Biobank dataset:OR=0.993,95%CI:0.987～0.999,P=0.014).This association remained robust in multivariable analysis(OR=0.992,95%CI:0.984～1.000,P=0.045).In contrast,other lipid metabolism markers did not demonstrate significant independent causal effects.Furthermore,while the protective effect of HDL-C in the Global Lipids Genetic Consortium dataset exhibited a similar trend,it did not reach statistical significance(OR=0.994,95%CI:0.987～1.000,P=0.054).Multivariable MR results also showed a marginal association(OR=0.992,95%CI:0.983～1.000,P=0.064).Conclusions HDL-C exhibits a protective role against hearing difficulty in noise.Improving HDL-C levels may positively impact hearing health by mechanisms such as suppressing inflammation,exerting antioxidant effects and improving microcirculation.