Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss

Show full item record



Permalink

http://hdl.handle.net/10138/346515

Citation

Estonian Biobank Res Team , Trpchevska , N , Freidin , M B , Broer , L , Kaprio , J , Kettunen , J & Mäkitie , A 2022 , ' Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss ' , American Journal of Human Genetics , vol. 109 , no. 6 , pp. 1077-1091 . https://doi.org/10.1016/j.ajhg.2022.04.010

Title: Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss
Author: Estonian Biobank Res Team; Trpchevska, Natalia; Freidin, Maxim B.; Broer, Linda; Kaprio, Jaakko; Kettunen, Johannes; Mäkitie, Antti
Contributor organization: Institute for Molecular Medicine Finland
University of Helsinki
HUS Head and Neck Center
Department of Ophthalmology and Otorhinolaryngology
Clinicum
Genetic Epidemiology
Genomics of Neurological and Neuropsychiatric Disorders
Complex Disease Genetics
Date: 2022-06-02
Language: eng
Number of pages: 16
Belongs to series: American Journal of Human Genetics
ISSN: 0002-9297
DOI: https://doi.org/10.1016/j.ajhg.2022.04.010
URI: http://hdl.handle.net/10138/346515
Abstract: Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss.
Subject: LD SCORE REGRESSION
GANGLION NEURONS
HAIR-CELLS
GWAS DATA
NOISE
PATHOGENICITY
HERITABILITY
INNER
DIFFERENTIATION
DEGENERATION
1184 Genetics, developmental biology, physiology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


Files in this item

Total number of downloads: Loading...

Files Size Format View
1_s2.0_S0002929722001586_main.pdf 4.782Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record