In a new genome-wide association study, an international team led by Keck Medicine of the University of Southern California (USC) neuroscientists has found evidence that some people may be more genetically susceptible to noise-induced hearing loss than others.
Noise-induced hearing loss is one of the most common work-related illnesses in the United States, according to the National Institute for Occupational Safety and Health. At especially high risk are troops in the Armed Forces. In 2013, the Department of Veterans Affairs reported hearing loss as one of the most common disabilities among veterans receiving disability compensation.
Those at higher, genetic risk for hearing loss may decide to take additional precautionary measures to protect their hearing prior to hazardous noise exposure, study authors say.
“Understanding the biological processes that affect susceptibility to hearing loss due to loud noise exposure is an important factor in reducing the risk,” said Keck Medicine of USC otologist Rick A. Friedman, M.D., Ph.D., professor of otolaryngology and neurosurgery at the Keck School of Medicine of USC and senior author of the study. “We have made great advances in hearing restoration, but nothing can compare to protecting the hearing you have and preventing hearing loss in the first place.”
The study, “Genome-wide association study identifies Nox3 as a critical gene for susceptibility to noise-induced hearing loss,” appears in the April 16 edition of PLOS Genetics, a peer-reviewed scientific journal.
While some gene association studies on noise-induced hearing loss in people have been conducted in the past, all were very small and their results un-replicated. Genome-wide association studies, or GWAS, search the entire genome for common genetic variants to see if any of those variants are associated with a trait. Mouse GWAS have lead to the discovery of hundreds of genes involved in complex traits that have immediate relevance to people.
In the USC study, conducted at the Zilkha Neurogenetic Institute, Friedman’s team identified the Nox3 gene, which is almost exclusively expressed in the inner ear, as a key gene for susceptibility to noise-induced hearing loss. Using 64 of the 100 strains of mice in the Hybrid Mouse Diversity Panel, the team was able to increase the statistical power of its investigation, leading to the first published GWAS for noise-induced hearing loss in mice.
More research is necessary before clinical recommendations can be made.
The study was conducted in collaboration with scientists from Brazil’s Federal University of Rio Grande do Sul and UCLA. Other Keck School of Medicine of USC authors include Joel Lavinsky, Amanda L. Crow, Juemei Wang, Ksenia A. Aaron, Maria K. Ho, Qingzhong Li, Pehzman Salehide, Anthon Myint and Maya Monges-Hernadez.
Funding: The study was supported in part by the National Institutes of Health (R01DC010856-01,T32ES013678, R01ES021801, 3R01ES021801-03S1, UL1TR000130, P30ES007048, R01 ES022282), California Institute for Regenerative Medicine (TG2-01161) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (7342-13-6).
This article was submitted directly to NeuroscienceNews.com by Alison Trinidad. We would like to thank her for this submission and her continued support.
Written by Alison Trinidad
Source: Keck Medicine/USC
Image Source: The image is credited to Rick A. Friedman Lab
Original Research: Full open access research for “Genome-Wide Association Study Identifies Nox3 as a Critical Gene for Susceptibility to Noise-Induced Hearing Loss” by Joel Lavinsky, Amanda L. Crow, Calvin Pan, Juemei Wang, Ksenia A. Aaron, Maria K. Ho, Qingzhong Li, Pehzman Salehide, Anthony Myint, Maya Monges-Hernadez, Eleazar Eskin, Hooman Allayee, Aldons J. Lusis, and Rick A. Friedman in PLOS Genetics. Published online April 16 2015 doi:10.1371/journal.pgen.1005094
Genome-Wide Association Study Identifies Nox3 as a Critical Gene for Susceptibility to Noise-Induced Hearing Loss
In the United States, roughly 10% of the population is exposed daily to hazardous levels of noise in the workplace. Twin studies estimate heritability for noise-induced hearing loss (NIHL) of approximately 36%, and strain specific variation in sensitivity has been demonstrated in mice. Based upon the difficulties inherent to the study of NIHL in humans, we have turned to the study of this complex trait in mice. We exposed 5 week-old mice from the Hybrid Mouse Diversity Panel (HMDP) to a 10 kHz octave band noise at 108 dB for 2 hours and assessed the permanent threshold shift 2 weeks post exposure using frequency specific stimuli. These data were then used in a genome-wide association study (GWAS) using the Efficient Mixed Model Analysis (EMMA) to control for population structure. In this manuscript we describe our GWAS, with an emphasis on a significant peak for susceptibility to NIHL on chromosome 17 within a haplotype block containing NADPH oxidase-3 (Nox3). Our peak was detected after an 8 kHz tone burst stimulus. Nox3 mutants and heterozygotes were then tested to validate our GWAS. The mutants and heterozygotes demonstrated a greater susceptibility to NIHL specifically at 8 kHz both on measures of distortion product otoacoustic emissions (DPOAE) and on auditory brainstem response (ABR). We demonstrate that this sensitivity resides within the synaptic ribbons of the cochlea in the mutant animals specifically at 8 kHz. Our work is the first GWAS for NIHL in mice and elucidates the power of our approach to identify tonotopic genetic susceptibility to NIHL.
“Genome-Wide Association Study Identifies Nox3 as a Critical Gene for Susceptibility to Noise-Induced Hearing Loss” by Joel Lavinsky, Amanda L. Crow, Calvin Pan, Juemei Wang, Ksenia A. Aaron, Maria K. Ho, Qingzhong Li, Pehzman Salehide, Anthony Myint, Maya Monges-Hernadez, Eleazar Eskin, Hooman Allayee, Aldons J. Lusis, and Rick A. Friedman in PLOS Genetics. Published online April 16 2015 doi:10.1371/journal.pgen.1005094