Association Analysis of Candidate Gene Polymorphisms and Tinnitus in Young Musicians

Subjective tinnitus, a perception of phantom sound, is a common otological condition that affects almost 15% of the general population. It is known that noise-induced hearing loss (NIHL) and tinnitus exhibit a high level of comorbidity in individuals exposed to intense noise and music. However, the influence of genetic variants associated with NIHL on tinnitus remains elusive. We hypothesized that young musicians carrying genetic variants associated with NIHL would exhibit a higher prevalence of tinnitus than their counterparts.

To test this hypothesis, we analyzed the database by Bhatt et al. (2020) (originally developed by Phillips et al., 2015) that investigated the genetic links to NIHL in young college-aged musicians. The present study identified 186 participants (average age = 20.3 yrs, range = 18-25 yrs) with normal tympanometry and otoscopic findings and with no missing data. We included 19 single nucleotide polymorphisms in 13 cochlear genes that were previously associated with NIHL. The candidate genes include: KCNE1, KCNQ1, CDH23, GJB2, GJB4, KCNJ10, CAT, HSP70, PCDH70, MYH14, GRM7, PON2, and ESRRB.

We find that individuals with at least one minor allele of rs163171 (C > T) in KCNQ1 exhibit significantly higher odds of reporting tinnitus compared to individuals carrying the major allele of rs163171. KCNE1 rs2070358 revealed a suggestive association (p = 0.049) with tinnitus, but the FDR corrected p-value did not achieve statistical significance (p < 0.05). A history of ear infection and sound level tolerance showed a statistically significant association with tinnitus. Music exposure showed a suggestive association trend with tinnitus. Biological sex revealed a statistically significant association with distortion product otoacoustic emissions SNR measures.

We concluded that KCNQ1/KCNE1 voltage-gated potassium ion channel plays a critical role in the pathogenesis of NIHL and tinnitus. Further research is required to construct clinical tools for identifying genetically predisposed individuals well before they acquire NIHL and tinnitus.