Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss
Natalia Trpchevska, Maxim B. Freidin, Linda Broer, Berthe C. Oosterloo, Shuyang Yao, Yitian Zhou, Barbara Vona, Charles E. Bishop, Argyro Bizaki-Vallaskangas, Barbara Canlon, Fabio Castellana, Daniel I. Chasman, Stacey S. Cherny, Kaare Christensen, Maria Pina Concas, Adolfo Correa, Ran Elkon, Andres Metspalu, Mari Nelis, Reedik Mägi, Tōnu Esko, Jonas Mengel‐From, Yan Gao, Anne B.S. Giersch, Giorgia Girotto, Alexander Guðjónsson, Vilmundur Guðnason, Nancy L. Heard‐Costa, Ronna Hertzano, Jacob Hjelmborg, Jens Hjerling‐Leffler, Howard J. Hoffman, Jaakko Kaprio, Johannes Kettunen, Kristi Krebs, Anna K. Kähler, François Lallemend, Lenore J. Launer, I‐Min Lee, Hampton L. Leonard, Chuan-Ming Li, Hubert Löwenheim, Patrik K. E. Magnusson, Joyce B. J. van Meurs, Lili Milani, Cynthia C. Morton, Antti Mäkitie, Mike A. Nalls, Giuseppe Giovanni Nardone, Marianne Nygaard, Teemu Palviainen, Sheila R. Pratt, Nicola Quaranta, Joel Rämö, Elmo Saarentaus, Rodolfo Sardone, Claudia L. Satizábal, John M. Schweinfurth, Sudha Seshadri, Eric J. Shiroma, Eldad D. Shulman, Eleanor M. Simonsick, Christopher Spankovich, Anke Tropitzsch, Volker M. Lauschke, Patrick F. Sullivan, André Goedegebure, Christopher R. Cederroth, Frances M. K. Williams, A. Paul Nagtegaal
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.