Abstract
To date, the knowledge of the genetic determinants behind the modulation of hearing ability is relatively limited. To investigate this trait, we performed Genome-Wide Association Study (GWAS) meta-analysis using genotype and audiometric data (hearing thresholds at 0.25, 0.5, 1, 2, 4, and 8 kHz, and pure-tone averages of thresholds at low, medium, and high frequencies) collected in nine cohorts from Europe, South-Eastern USA, Caucasus, and Central Asia, for an overall number of ~9000 subjects. Three hundred seventy-five genes across all nine analyses were tagged by single nucleotide polymorphisms (SNPs) reaching a suggestive p-value (p < 10−5). Amongst these, 15 were successfully replicated using a gene-based approach in the independent Italian Salus in the Apulia cohort (n = 1774) at the nominal significance threshold (p < 0.05). In addition, the expression level of the replicated genes was assessed in published human and mouse inner ear datasets. Considering expression patterns in humans and mice, eleven genes were considered particularly promising candidates for the hearing function: BNIP3L, ELP5, MAP3K20, MATN2, MTMR7, MYO1E, PCNT, R3HDM1, SLC9A9, TGFB2, and YTHDC2. These findings represent a further contribution to our understanding of the genetic basis of hearing function and its related diseases.
Highlights
One of the most complex mechanisms in humans is the sense of hearing, which has become a cornerstone of our communication, integration, and sociality [1]
We used audiometric and genetic data from ten different cohorts to investigate the genetic determinants of hearing function through a multistep approach
A replication phase was carried out using a gene-based approach; in the final phase, we used a published RNA-seq human inner ear dataset [29] and mouse microarray expression data [30] to assess the expression levels of the genes of interest identified in the previous steps
Summary
One of the most complex mechanisms in humans is the sense of hearing, which has become a cornerstone of our communication, integration, and sociality [1]. At the base of this fundamental ability is the auditory system, an intricate apparatus aimed at converting mechanical soundwaves into electrical impulses that the brain can process [1]. Due to its location, it is possible to take tissue samples from the auditory system in small quantities and only in particular cases. Biochemical approaches similar to those used to study the visual and olfactory system have limited effectiveness. Genetic approaches, such as nextgeneration sequencing of patients affected by hearing loss or Genome-Wide Association
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
