Causal associations of white blood cell subtypes with age-related hearing loss: A Mendelian randomization study

While elevated white blood cell (WBC) counts are associated with auditory decline, the causal nature of this relationship remains elusive due to potential residual confounding. We utilized 2-sample Mendelian randomization (MR) to assess potential causal relationships between 5 genetically predicted WBC subtypes and the risk of age-related (ARHL) and sensorineural hearing loss. Two-sample MR analyses were conducted using summary statistics from large-scale genome-wide association studies. Causal estimates were assessed via inverse variance weighted, weighted median, weighted mode, and MR-Egger regression methods. Robustness was verified through extensive sensitivity analyses, including Cochran's Q tests, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), Radial MR, and leave-one-out tests, to detect heterogeneity and horizontal pleiotropy. Genetically predicted higher neutrophil counts were significantly associated with a reduced risk of ARHL (odds ratio [OR] = 0.9765, 95% confidence intervals [CI] = 0.9646-0.9886, P = .0002, false discovery rate [FDR] = 0.0015). Nominally significant protective associations were also observed for higher eosinophil (OR = 0.9883, 95% CI = 0.9777-0.9991, P = .0344, FDR = 0.1148) and lymphocyte counts (OR = 0.9858; 95% CI = 0.9745-0.9972, P = .0148, FDR = 0.0739). No significant heterogeneity or pleiotropy was detected in the final analyses for these associations. No causal associations were found between any WBC counts and sensorineural hearing loss. MR Steiger tests confirmed the consistency in causal directions. This MR study provides genetic evidence for a causal protective association between higher neutrophil counts and a reduced risk of ARHL. The potential roles of eosinophils and lymphocytes in ARHL warrant further investigation.