Evidence map›Paper›PMID 25880434›Full record

ArticlePLoS genetics2015

Genome-wide association study identifies nox3 as a critical gene for susceptibility to noise-induced hearing loss.

Joel Lavinsky, Amanda L Crow, Calvin Pan, Juemei Wang, Ksenia A Aaron, Maria K Ho, Qingzhong Li, Pehzman Salehide, Anthony Myint, Maya Monges-Hernadez and 4 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.

  1. Pooled it
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  5. Article
  6. Article
  7. NADPH Oxidase 3: Beyond the Inner Ear.Antioxidants (Basel, Switzerland) · 2024
    Review
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  20. Large-scale phenotyping of ABR P1-N1 amplitudes before and after exposure to noise in 69 strains of mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2021
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 2 countries.

Joel LavinskyGraduate Program in Surgical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Department of Otolaryngology, Zilkha Neurogenetic Institute, USC Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
Amanda L CrowDepartment of Preventive Medicine and Institute for Genetic Medicine, USC Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
Calvin PanDepartment of Human Genetics, University of California, Los Angeles, Los Angeles, California, United States of America.
Juemei WangDepartment of Otolaryngology, Zilkha Neurogenetic Institute, USC Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
Ksenia A AaronDepartment of Otolaryngology, Zilkha Neurogenetic Institute, USC Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
Maria K HoDepartment of Otolaryngology, Zilkha Neurogenetic Institute, USC Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
Qingzhong LiDepartment of Otolaryngology, Zilkha Neurogenetic Institute, USC Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
Pehzman SalehideDepartment of Otolaryngology, Zilkha Neurogenetic Institute, USC Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
Anthony MyintDepartment of Otolaryngology, Zilkha Neurogenetic Institute, USC Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
Maya Monges-HernadezDepartment of Otolaryngology, Zilkha Neurogenetic Institute, USC Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
Eleazar EskinDepartment of Computer Science, University of California, Los Angeles, Los Angeles, California, United States of America.
Hooman AllayeeDepartment of Human Genetics, University of California, Los Angeles, Los Angeles, California, United States of America.
Aldons J LusisDepartment of Preventive Medicine and Institute for Genetic Medicine, USC Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, United States of America.
Rick A FriedmanDepartment of Otolaryngology, Zilkha Neurogenetic Institute, USC Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
University of Southern California · USUniversity of California, Los Angeles · USUniversidade Federal do Rio Grande do Sul · BR

Funding

Translational Research Support CoreP30ES007048 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ROB S MCCONNELL · 1996 to 2026
$46.4M
Southern California Clinical and Translational Science InstituteUL1TR000130 · NCATS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BUCHANAN, THOMAS A · 2012 to 2015
$36.0M
Training Grant in Genomic Analysis and InterpretationT32ES013678 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GAUDERMAN, WILLIAM JAMES, MCCONNELL, ROB S · 2006 to 2023
$5.6M
INTEGRATIVE GENETIC APPROACHES TO GENE-AIR POLLUTION INTERACTIONS IN ASTHMAR01ES021801 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI AKBARI, OMID, ALLAYEE, HOOMAN · 2012 to 2016
$3.9M
High-Resolution Mapping of Susceptibility Genes for NIHLR01DC010856 · NIDCD · UNIVERSITY OF SOUTHERN CALIFORNIA · PI FRIEDMAN, RICK A · 2011 to 2015
$2.2M
Correcting for Population Structure in Gene-by-Environment Interaction StudiesR01ES022282 · NIEHS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ESKIN, ELEAZAR · 2013 to 2015
$1.2M
NCATS NIH HHS UL1 TR000130NCATS NIH HHS UL1TR000130NIDCD NIH HHS R01 DC010856NIDCD NIH HHS R01DC010856-01NIEHS NIH HHS 3R01ES021801-03S1NIEHS NIH HHS P30 ES007048NIEHS NIH HHS P30ES007048NIEHS NIH HHS R01 ES021801NIEHS NIH HHS R01ES021801NIEHS NIH HHS R01 ES022282NIEHS NIH HHS T32 ES013678NIEHS NIH HHS T32ES013678
6 · The paper itself

Abstract

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.

Indexed as

AnimalsEvoked Potentials, AuditoryGenome-Wide Association StudyHearing Loss, Noise-InducedHeterozygoteMiceMice, Inbred C57BLMutationNADPH OxidasesNADPH OxidasesNox3 protein, mouse

Identifiers

PMID25880434
PMCPMC4399881
OpenAlexW2040023298

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.