The Genetic Architecture of Noise-Induced Hearing Loss: Evidence for a Gene-by-Environment Interaction
Year: 2016
Type: article
Abstract: The discovery of environmentally specific genetic effects is crucial to the understanding of complex traits, such as susceptibility to noise-induced hearing loss (NIHL). We describe the first genome-wide association study (GWAS) for NIHL in a large and well-characterized population of inbred mouse strains, known as the Hybrid Mouse Diversity Panel (HMDP). We recorded auditory brainstem response (ABR) thresholds both pre and post 2-hr exposure to 10-kHz octave band noise at 108 dB sound pressure level in 5-6-wk-old female mice from the HMDP (4-5 mice/strain). From the observation that NIHL susceptibility varied among the strains, we performed a GWAS with correction for population structure and mapped a locus on chromosome 6 that was statistically significantly associated with two adjacent frequencies. We then used a "genetical genomics" approach that included the analysis of cochlear eQTLs to identify candidate genes within the GWAS QTL. In order to validate the gene-by-environment interaction, we compared the effects of the postnoise exposure locus with that from the same unexposed strains. The most significant SNP at chromosome 6 (rs37517079) was associated with noise susceptibility, but was not significant at the same frequencies in our unexposed study. These findings demonstrate that the genetic architecture of NIHL is distinct from that of unexposed hearing levels and provide strong evidence for gene-by-environment interactions in NIHL.
Source: G3 Genes Genomes Genetics
Language: English
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,709
Funders: California Institute for Regenerative Medicine, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, National Institutes of Health, National Institute on Deafness and Other Communication Disorders, National Institute of Environmental Health Sciences, National Center for Advancing Translational Sciences
Awards: Environmental Genomics, Southern California Clinical and Translational Science Institute, Correcting for Population Structure in Gene-by-Environment Interaction Studies, High-Resolution Mapping of Susceptibility Genes for NIHL, CIRM Stem Cell Biology Training Program, INTEGRATIVE GENETIC APPROACHES TO GENE-AIR POLLUTION INTERACTIONS IN ASTHMA, Environmental Exposures, Host Factors and Human Disease
OpenAlex ID: W2513271077