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

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...

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Detalles Bibliográficos
Autores principales: Trpchevska, Natalia, Freidin, Maxim B., Broer, Linda, Oosterloo, Berthe C., Yao, Shuyang, Zhou, Yitian, Vona, Barbara, Bishop, Charles, Bizaki-Vallaskangas, Argyro, Canlon, Barbara, Castellana, Fabio, Chasman, Daniel I., Cherny, Stacey, Christensen, Kaare, Concas, Maria Pina, Correa, Adolfo, Elkon, Ran, Mengel-From, Jonas, Gao, Yan, Giersch, Anne B.S., Girotto, Giorgia, Gudjonsson, Alexander, Gudnason, Vilmundur, Heard-Costa, Nancy L., Hertzano, Ronna, Hjelmborg, Jacob v.B., Hjerling-Leffler, Jens, Hoffman, Howard J., Kaprio, Jaakko, Kettunen, Johannes, Krebs, Kristi, Kähler, Anna K., Lallemend, Francois, Launer, Lenore J., Lee, I-Min, Leonard, Hampton, Li, Chuan-Ming, Lowenheim, Hubert, Magnusson, Patrik K.E., van Meurs, Joyce, Milani, Lili, Morton, Cynthia C., Mäkitie, Antti, Nalls, Mike A., Nardone, Giuseppe Giovanni, Nygaard, Marianne, Palviainen, Teemu, Pratt, Sheila, Quaranta, Nicola, Rämö, Joel, Saarentaus, Elmo, Sardone, Rodolfo, Satizabal, Claudia L., Schweinfurth, John M., Seshadri, Sudha, Shiroma, Eric, Shulman, Eldad, Simonsick, Eleanor, Spankovich, Christopher, Tropitzsch, Anke, Lauschke, Volker M., Sullivan, Patrick F., Goedegebure, Andre, Cederroth, Christopher R., Williams, Frances M.K., Nagtegaal, Andries Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247887/
https://www.ncbi.nlm.nih.gov/pubmed/35580588
http://dx.doi.org/10.1016/j.ajhg.2022.04.010
Descripción
Sumario: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.