Sarcopenia and Risk of Hearing Loss: A 2-Sample Mendelian Randomization Study

We read with great interest where a prospective cohort study by Kawakami et al1Kawakami R Sawada SS Kato K et al.A prospective cohort study of muscular and performance fitness and risk of hearing loss: the Niigata wellness study.Am J Med. 2021; 134: 235-242.e234https://doi.org/10.1016/j.amjmed.2020.06.021Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar commented that muscle strength is associated with hearing loss in Japanese subjects. An observational study previously linked muscle mass to hearing loss.2Lee J Han K Song JJ et al.Sarcopenia and hearing loss in older Koreans: findings from the Korea National Health and Nutrition Examination Survey (KNHANES) 2010.PloS One. 2016; 11e0150281https://doi.org/10.1371/journal.pone.0150281Crossref Scopus (15) Google Scholar Both muscle mass and muscle strength belong to sarcopenia phenotypes. However, the association of sarcopenia with hearing loss needs to be further determined; due to the cohort study it is difficult to isolate residual confounders and the limitations of the race and size of the study population. Mendelian randomization (MR) analysis uses genetic variation as an instrumental variable to estimate causal effects, and results are not affected by confounding factors. Here, we leveraged data from large-scale genetic association studies in European populations and applied 2-sample MR analyses to investigate the causal relationship between sarcopenia and 4 hearing loss subtypes: sensorineural hearing loss (SNHL), sudden sensorineural hearing loss (SSHL), conductive hearing loss (CHL), mixed hearing loss (MHL). We used the summary-level genetic data for 3 sarcopenia-associated traits from UK Biobank (UKB), namely hand grip strength (right and left), walking pace, and appendicular lean mass (female and male). Genome-wide association study (GWAS) data of 3 hearing loss subtypes from the FinnGen without UKB's participants were available for 15,952 sensorineural hearing losses, 1491 sudden sensorineural hearing losses, 1255 conductive hearing losses, 1863 mixed hearing losses, and 196,592 controls. All GWAS summary statistics can be downloaded from the IEU OpenGWAS project (https://gwas.mrcieu.ac.uk/). The MR analysis were performed using the inverse-variance weighted method. Cochran's Q statistic, the MR-Egger intercept test, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) were performed, which can estimate heterogeneity and horizontal pleiotropy. Single-nucleotide polymorphisms at P < 5 × 10−8 were selected as instrumental variables. The linkage disequilibrium threshold was set to r2 = 0.001 within a distance of 10,000 kb. The MR analysis (Figure) showed that the negative causality between walking pace and sensorineural hearing loss (odds ratio [OR] = 0.531 [95% confidence interval [CI], 0.305-0.927], P value = .026), sudden sensorineural hearing loss (OR = 0.185 [95% CI, 0.052-0.665], P value = .009); hand grip strength (right) and conductive hearing loss (OR = 0.413 [95% CI, 0.211-0.806], P value =.009); and appendicular lean mass and mixed hearing loss (OR = 0.847 [95% CI, 0.731-0.982], P value = .028). Notably, we found a causal relationship between appendicular lean mass in female and mixed hearing loss (OR = 0.832 [95% CI, 0.713-0.971], P value = .019) but not in males (P value > .05). There was neither heterogeneity or horizontal pleiotropy in MR estimates (Cochranes's Q P value > .05, MR-PRESSO Global Test P value > .05, and MR-Egger intercept P value > 0.05). In conclusion, this MR study provided evidence for the association of sarcopenia with hearing loss, suggesting the impact of sarcopenia on the development of hearing loss.