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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\u20136-wk-old female mice from the HMDP (4\u20135 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 \u201cgenetical genomics\u201d 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.<\/jats:p>","DOI":"10.1534\/g3.116.032516","type":"journal-article","created":{"date-parts":[[2016,8,12]],"date-time":"2016-08-12T23:03:50Z","timestamp":1471043030000},"page":"3219-3228","source":"Crossref","is-referenced-by-count":27,"title":["The Genetic Architecture of Noise-Induced Hearing Loss: Evidence for a Gene-by-Environment Interaction"],"prefix":"10.1093","volume":"6","author":[{"given":"Joel","family":"Lavinsky","sequence":"first","affiliation":[{"name":"Tina and Rick Caruso Department of Otolaryngology, Zilkha Neurogenetic Institute"},{"name":"Graduate Program in Surgical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marshall","family":"Ge","sequence":"additional","affiliation":[{"name":"Tina and Rick Caruso Department of Otolaryngology, Zilkha Neurogenetic Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda L","family":"Crow","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine and Institute for Genetic Medicine, USC Keck School of Medicine, University of Southern California, Los Angeles, California 90033"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Calvin","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Human Genetics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juemei","family":"Wang","sequence":"additional","affiliation":[{"name":"Tina and Rick Caruso Department of Otolaryngology, Zilkha Neurogenetic Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pezhman","family":"Salehi","sequence":"additional","affiliation":[{"name":"Tina and Rick Caruso Department of Otolaryngology, Zilkha Neurogenetic Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Myint","sequence":"additional","affiliation":[{"name":"Tina and Rick Caruso Department of Otolaryngology, Zilkha Neurogenetic Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleazar","family":"Eskin","sequence":"additional","affiliation":[{"name":"Department of Computer Science"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hooman","family":"Allayee","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine and Institute for Genetic Medicine, USC Keck School of Medicine, University of Southern California, Los Angeles, California 90033"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aldons J","family":"Lusis","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90024"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rick A","family":"Friedman","sequence":"additional","affiliation":[{"name":"Tina and Rick Caruso Department of Otolaryngology, Zilkha Neurogenetic Institute"},{"name":"Tina and Rick Caruso Department of Otolaryngology, Zilkha Neurogenetic Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,10,1]]},"reference":[{"issue":"2","key":"2021042018231396700_bib1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1101\/gr.099234.109","article-title":"A high-resolution association mapping panel for the dissection of complex traits in mice","volume":"20","author":"Bennett","year":"2010","journal-title":"Genome Res."},{"issue":"7","key":"2021042018231396700_bib2","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1097\/00043764-199307000-00009","article-title":"The purposes of occupational medical surveillance in US industry and related health findings.","volume":"35","author":"Conway","year":"1993","journal-title":"J. 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