Feasibility of a bilateral 4000–6000 Hz notch as a phenotype for genetic association analysis

Abstract

Objective: Noise-induced hearing loss (NIHL) is a worldwide health problem and a growing concern among young people. Although some people appear to be more susceptible to NIHL, genetic association studies lack a specific phenotype. We tested the feasibility of a bilateral 4000–6000 Hz audiometric notch as a phenotype for identifying genetic contributions to hearing loss in young adults. Design: A case-control-control study was conducted to examine selected SNPs in 52 genes previously associated with hearing loss and/or expressed in the cochlea. A notch was defined as a minimum of a 15-dB drop at 4000–6000 Hz from the previous best threshold with a 5-dB ‘recovery’ at 8000 Hz. Study sample: Participants were 252 individuals of European descent taken from a population of 640 young adults who are students of classical music. Participants were grouped as No-notch (NN), Unilateral Notch (UN), or Bilateral Notch (BN). Results: The strongest evidence of a genetic association with the 4000–6000 Hz notch was a nonsynonymous SNP variant in the ESRR– gene (rs61742642:C> T, P386S). Carriers of the minor allele accounted for 26% of all bilateral losses. Conclusion: This study indicates that the 4000–6000 Hz bilateral notch is a feasible phenotype for identifying genetic susceptibility to hearing loss.

Key Words::

• Hearing conservation
• syndromes/genetics
• noise
• medical audiology

Acknowledgements

This work is supported by the National Institutes of Deafness and other Communication Disorders grant R21DC009296-01. We also thank the Music Research Institute and the Center for Biotechnology, Genomics, and Health Research for their support. We also acknowledge the contributions of Leslie Simmons and Sara Hunt for assistance with data collection, Jenna Callendar, Renuka Shivaji and Rohini Patel for technical assistance with the preparation and processing of DNA samples, and Jeong Sep Sihm for assistance with survey database management and analysis.

Declaration of interest: The authors declare no conflicts of interest.

Supplementary material available online

Supplementary Tables 1 to 3 and Figure 1, available online at http://informahealthcare.com/doi/abs/10.3109/14992027.2015.1030512.