A combined genome-wide association and molecular study of age-related hearing loss in H. sapiens.

Cochlea Genome-Wide Association Study Hearing Loss / genetics Hearing Loss, Sensorineural Humans Phenotype Trans-Activators / genetics Ubiquitin-Protein Ligases
Age-related hearing loss GWAS Human gene expression Structured illumination microscopy

Journal

BMC medicine
ISSN: 1741-7015
Titre abrégé: BMC Med
Pays: England
ID NLM: 101190723

Informations de publication

Date de publication:
01 12 2021
Historique:
received: 11 07 2021
accepted: 21 10 2021
entrez: 1 12 2021
pubmed: 2 12 2021
medline: 27 1 2022
Statut: epublish

Résumé

Sensorineural hearing loss is one of the most common sensory deficiencies. However, the molecular contribution to age-related hearing loss is not fully elucidated. We performed genome-wide association studies (GWAS) for hearing loss-related traits in the UK Biobank (N = 362,396) and selected a high confidence set of ten hearing-associated gene products for staining in human cochlear samples: EYA4, LMX1A, PTK2/FAK, UBE3B, MMP2, SYNJ2, GRM5, TRIOBP, LMO-7, and NOX4. All proteins were found to be expressed in human cochlear structures. Our findings illustrate cochlear structures that mediate mechano-electric transduction of auditory stimuli, neuronal conductance, and neuronal plasticity to be involved in age-related hearing loss. Our results suggest common genetic variation to influence structural resilience to damage as well as cochlear recovery after trauma, which protect against accumulated damage to cochlear structures and the development of hearing loss over time.

Sections du résumé

BACKGROUND
Sensorineural hearing loss is one of the most common sensory deficiencies. However, the molecular contribution to age-related hearing loss is not fully elucidated.
METHODS
We performed genome-wide association studies (GWAS) for hearing loss-related traits in the UK Biobank (N = 362,396) and selected a high confidence set of ten hearing-associated gene products for staining in human cochlear samples: EYA4, LMX1A, PTK2/FAK, UBE3B, MMP2, SYNJ2, GRM5, TRIOBP, LMO-7, and NOX4.
RESULTS
All proteins were found to be expressed in human cochlear structures. Our findings illustrate cochlear structures that mediate mechano-electric transduction of auditory stimuli, neuronal conductance, and neuronal plasticity to be involved in age-related hearing loss.
CONCLUSIONS
Our results suggest common genetic variation to influence structural resilience to damage as well as cochlear recovery after trauma, which protect against accumulated damage to cochlear structures and the development of hearing loss over time.

Identifiants

DOI: 10.1186/s12916-021-02169-0 PMID: 34847940 PMC: PMC8638543
pubmed: 34847940
doi: 10.1186/s12916-021-02169-0
pii: 10.1186/s12916-021-02169-0
pmc: PMC8638543
doi:

Substances chimiques

EYA4 protein, human 0
Trans-Activators 0
UBE3B protein, human EC 2.3.2.26
Ubiquitin-Protein Ligases EC 2.3.2.27

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

302

Subventions

Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom

Informations de copyright

© 2021. The Author(s).

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Auteurs

Wei Liu (W)

Department of Surgical Sciences, Section of Otorhinolaryngology and Head & Neck Surgery, Uppsala University, SE-751 85, Uppsala, Sweden.

Åsa Johansson (Å)

Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Helge Rask-Andersen (H)

Department of Surgical Sciences, Section of Otorhinolaryngology and Head & Neck Surgery, Uppsala University, SE-751 85, Uppsala, Sweden. helge.rask-andersen@surgsci.uu.se.

Mathias Rask-Andersen (M)

Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. mathias.rask-andersen@igp.uu.se.
ORCID: 0000-0002-8008-4659

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Classifications MeSH

questionsmedicales.fr › Organes des sens › Oreille › Oreille interne › Cochlée › A combined genome-wide association and...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › A combined genome-wide association and...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Troubles sensitifs › Troubles de l'audition › Perte d'audition › A combined genome-wide association and...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Troubles sensitifs › Troubles de l'audition › Perte d'audition › Surdité neurosensorielle › A combined genome-wide association and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › A combined genome-wide association and...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › A combined genome-wide association and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Protéines virales régulatrices ou accessoires › Transactivateurs › A combined genome-wide association and...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Ligases › Ubiquitin-protein ligase complexes › Ubiquitin-protein ligases › A combined genome-wide association and...