Evidence map›Paper›PMID 40399499›Full record

ArticleJournal of the Association for Research in Otolaryngology : JARO2025

Genome-Wide Association Study of Age-Related Hearing Loss in CFW Mice Identifies Multiple Genes and Loci, Including Prkag2.

Oksana Polesskaya, Ely Boussaty, Riyan Cheng, Olivia A Lamonte, Thomas Y Zhou, Eric Du, Thiago Missfeldt Sanches, Khai-Minh Nguyen, Mika Okamoto, Abraham A Palmer and 1 more

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Article in Journal of the Association for Research in Otolaryngology : JARO, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Oksana PolesskayaDepartment of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA. opolesskaya@ucsd.edu.ORCID http://orcid.org/0000-0003-3024-114X
Ely BoussatyDepartment of Otolaryngology - Head and Neck Surgery, University of California San Diego, La Jolla, CA, 92093, USA.
Riyan ChengDepartment of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA.
Olivia A LamonteDepartment of Otolaryngology - Head and Neck Surgery, University of California San Diego, La Jolla, CA, 92093, USA.
Thomas Y ZhouDepartment of Otolaryngology - Head and Neck Surgery, University of California San Diego, La Jolla, CA, 92093, USA.
Eric DuDepartment of Otolaryngology - Head and Neck Surgery, University of California San Diego, La Jolla, CA, 92093, USA.
Thiago Missfeldt SanchesDepartment of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA.
Khai-Minh NguyenDepartment of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA.
Mika OkamotoDepartment of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA.
Abraham A PalmerDepartment of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA.
Rick FriedmanDepartment of Otolaryngology - Head and Neck Surgery, University of California San Diego, La Jolla, CA, 92093, USA. rafriedman@health.ucsd.edu.

Funding

The genetic basis for age-related hearing loss in outbred miceR01DC018566 · NIDCD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FRIEDMAN, RICK A · 2020 to 2024
$2.7M
NIH HHS R01 DC018566
6 · The paper itself

Abstract

purposeAge-related hearing loss (ARHL) is one of the most prevalent conditions affecting the elderly. ARHL is influenced by a combination of environmental and genetic factors; the identification of the genes that confer risk will aid in the prevention and treatment of ARHL. The mouse and human inner ears are functionally and genetically homologous. We used Carworth Farms White (CFW) mice to study the genetic basis of ARHL because they are genetically diverse and exhibit variability in the age of onset and severity of ARHL.

methodsHearing at a range of frequencies was measured using auditory brainstem response (ABR) thresholds in 946 male and female CFW mice at the age of 1, 6, and 10 months. We genotyped the mice using low-coverage (mean coverage 0.27 ×) whole-genome sequencing (lcWGS) followed by imputation using STITCH. To determine the accuracy of the genotypes, we sequenced 8 samples at > 30 × coverage and used those data to estimate the accuracy of lcWGS genotyping, which was > 99.5%. We performed a genome-wide association study (GWAS) for the ABR thresholds for each frequency at each age, and we also performed a GWAS for age at deafness.

resultsWe obtained genotypes at 4.18 million single nucleotide polymorphisms (SNP). The SNP heritability for traits ranged from 0 to 42%. GWAS identified 10 significant associations with ARHL that contained potential candidate genes, including Dnah11, Rapgef5, Cpne4, Prkag2, and Nek11. Genetic ablation of Prkag2 caused ARHL at high frequencies, strongly suggesting that Prkag2 is the causal gene for one of the associations.

conclusionsGWAS for ARHL in CFW outbred mice identified genetic risk factors for ARHL, including Prkag2. Our results will help to define novel therapeutic targets for the treatment and prevention of this common disorder.

Indexed as

AMP-Activated Protein KinasesGenome-Wide Association StudyPresbycusisAnimalsEvoked Potentials, Auditory, Brain StemFemaleMaleMicePolymorphism, Single NucleotideAMP-Activated Protein KinasesABRAge-related hearing lossCFW outbred miceGWASPrkag2

Identifiers

PMID40399499
PMCPMC12411389

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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 OpenQuestion graph.