Untangling the genomics of noise-induced hearing loss and tinnitus: Contributions of Mus musculus and Homo sapiens

Abstract

Acoustic trauma is a feature of the industrial age, in general, and mechanized warfare, in particular. Noise-induced hearing loss (NIHL) and tinnitus have been the number 1 and number 2 disabilities at U.S. Veterans hospitals since 2006. In a reversal of original protocols to identify candidate genes associated with monogenic deafness disorders, unbiased genome-wide association studies now direct animal experiments in order to explore genetic variants common in Homo sapiens. However, even these approaches must utilize animal studies for validation of function and understanding of mechanisms. Animal research currently focuses on genetic expression profiles since the majority of variants occur in non-coding regions, implying regulatory divergences. Moving forward, it will be important in both human and animal research to define the phenotypes of hearing loss and tinnitus, as well as exposure parameters, in order to extricate genes related to acoustic trauma versus those related to aging. It has become clear that common disorders like acoustic trauma are influenced by large numbers of genes, each with small effects, which cumulatively lead to susceptibility to a disorder. A polygenic risk score, which aggregates these small effect sizes of multiple genes, may offer a more accurate description of risk for NIHL and/or tinnitus.

FIG. 1.

(Color online) Question on tinnitus from the UKB TouchScreen. In answer to the question regarding noises in the ear, participants answered according to seven categories shown. Figures in parentheses are numbers of participants who answered within that category.

FIG. 2.

(Color online) Manhattan plot of question on hearing loss from the United Kingdom cohort publicly available data. Participants answered “yes” or “no” to the question, “Do you have any difficulty with your hearing?.” Significant SNP hits are seen as a vertical line that extends above the accepted significance P-value of 5E-08. Significant genes are labeled, while those lines that are not labeled may indicate hits that fall outside of known genes.