TY - JOUR
T1 - Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss
AU - Estonian Biobank Research Team
AU - Trpchevska, Natalia
AU - Freidin, Maxim B.
AU - Broer, Linda
AU - Oosterloo, Berthe C.
AU - Yao, Shuyang
AU - Zhou, Yitian
AU - Vona, Barbara
AU - Bishop, Charles
AU - Bizaki-Vallaskangas, Argyro
AU - Canlon, Barbara
AU - Castellana, Fabio
AU - Chasman, Daniel I.
AU - Cherny, Stacey
AU - Christensen, Kaare
AU - Concas, Maria Pina
AU - Correa, Adolfo
AU - Elkon, Ran
AU - Metspalu, Andres
AU - Nelis, Mari
AU - Mägi, Reedik
AU - Esko, Tõnu
AU - Mengel-From, Jonas
AU - Gao, Yan
AU - Giersch, Anne B.S.
AU - Girotto, Giorgia
AU - Gudjonsson, Alexander
AU - Gudnason, Vilmundur
AU - Heard-Costa, Nancy L.
AU - Hertzano, Ronna
AU - Hjelmborg, Jacob v.B.
AU - Hjerling-Leffler, Jens
AU - Hoffman, Howard J.
AU - Kaprio, Jaakko
AU - Kettunen, Johannes
AU - Krebs, Kristi
AU - Kähler, Anna K.
AU - Lallemend, Francois
AU - Launer, Lenore J.
AU - Lee, I. Min
AU - Leonard, Hampton
AU - Li, Chuan Ming
AU - Lowenheim, Hubert
AU - Magnusson, Patrik K.E.
AU - van Meurs, Joyce
AU - Milani, Lili
AU - Morton, Cynthia C.
AU - Mäkitie, Antti
AU - Nalls, Mike A.
AU - Satizabal, Claudia L.
AU - Seshadri, Sudha
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/6/2
Y1 - 2022/6/2
N2 - 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.
AB - 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.
KW - ARHL
KW - GWAS
KW - basal cells
KW - cochlea
KW - genetics
KW - hair cells
KW - hearing loss
KW - root cells
KW - spindle cells
KW - stria vascularis
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U2 - 10.1016/j.ajhg.2022.04.010
DO - 10.1016/j.ajhg.2022.04.010
M3 - Article
C2 - 35580588
AN - SCOPUS:85131054928
SN - 0002-9297
VL - 109
SP - 1077
EP - 1091
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 6
ER -