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 Bishop; Argyro Bizaki-vallaskangas; Barbara Canlon; Fabio Castellana; Daniel I. Chasman; Stacey Cherny; Kaare Christensen; Maria Pina Concas; Adolfo Correa; Ran Elkon; Jonas Mengel-from; Yan Gao; Anne B.s. Giersch; Giorgia Girotto; Alexander Gudjonsson; Vilmundur Gudnason; Nancy L. Heard-costa; Ronna Hertzano; Jacob V.b. Hjelmborg; Jens Hjerling-leffler; Howard J. Hoffman; Jaakko Kaprio; Johannes Kettunen; Kristi Krebs; Anna K. Kähler; Francois Lallemend; Lenore J. Launer; I-min Lee; Hampton Leonard; Chuan-ming Li; Hubert Lowenheim; Patrik K.e. Magnusson; Joyce Van Meurs; Lili Milani; Cynthia C. Morton; Antti Mäkitie; Mike A. Nalls; Giuseppe Giovanni Nardone; Marianne Nygaard; Teemu Palviainen; Sheila Pratt; Nicola Quaranta; Joel Rämö; Elmo Saarentaus; Rodolfo Sardone; Claudia L. Satizabal; John M. Schweinfurth; Sudha Seshadri; Eric Shiroma; Eldad Shulman; Eleanor Simonsick; Christopher Spankovich; Anke Tropitzsch; Volker M. Lauschke; Patrick F. Sullivan; Andre Goedegebure; Christopher R. Cederroth; Frances M.k. Williams; Andries Paul Nagtegaal; Andres Metspalu; Mari Nelis; Reedik Mägi; Tõnu Esko

doi:10.1016/j.ajhg.2022.04.010

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 Bishop, Argyro Bizaki-vallaskangas, Barbara Canlon, Fabio Castellana, Daniel I. Chasman, Stacey Cherny, Kaare Christensen, Maria Pina Concas, Adolfo Correa, Ran Elkon, Jonas Mengel-from, Yan Gao, Anne B.s. GierschGiorgia Girotto, Alexander Gudjonsson, Vilmundur Gudnason, Nancy L. Heard-costa, Ronna Hertzano, Jacob V.b. Hjelmborg, Jens Hjerling-leffler, Howard J. Hoffman, Jaakko Kaprio, Johannes Kettunen, Kristi Krebs, Anna K. Kähler, Francois Lallemend, Lenore J. Launer, I-min Lee, Hampton Leonard, Chuan-ming Li, Hubert Lowenheim, Patrik K.e. Magnusson, Joyce Van Meurs, Lili Milani, Cynthia C. Morton, Antti Mäkitie, Mike A. Nalls, Giuseppe Giovanni Nardone, Marianne Nygaard, Teemu Palviainen, Sheila Pratt, Nicola Quaranta, Joel Rämö, Elmo Saarentaus, Rodolfo Sardone, Claudia L. Satizabal, John M. Schweinfurth, Sudha Seshadri, Eric Shiroma, Eldad Shulman, Eleanor Simonsick, Christopher Spankovich, Anke Tropitzsch, Volker M. Lauschke, Patrick F. Sullivan, Andre Goedegebure, Christopher R. Cederroth, Frances M.k. Williams, Andries Paul Nagtegaal, Andres Metspalu, Mari Nelis, Reedik Mägi, Tõnu Esko

Division of Human Communication, Development & Hearing (L5)

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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.

Original language	English
Journal	American Journal of Human Genetics
Early online date	16 May 2022
DOIs	https://doi.org/10.1016/j.ajhg.2022.04.010
Publication status	Published - 16 May 2022

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10.1016/j.ajhg.2022.04.010Licence: CC BY

mmc3Final published version, 13.5 MBLicence: CC BY

https://linkinghub.elsevier.com/retrieve/pii/S0002929722001586

Manchester Centre for Audiology and Deafness (ManCAD)
Munro, K., Millman, R., Lamb, W., Dawes, P., Plack, C., Stone, M., Kluk-De Kort, K., Moore, D., Morton, C., Prendergast, G., Couth, S., Schlittenlacher, J., Chilton, H., Visram, A., Dillon, H., Guest, H., Heinrich, A., Jackson, I., Littlejohn, J., Jones, L., Lough, M., Morgan, R., Perugia, E., Roughley, A., Whiston, H., Wright, C., Saunders, G., Kelly, C., Cross, H., Loughran, M. & Hoseinabadi, R.
Project: Research

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Trpchevska, N., Freidin, M. B., Broer, L., Oosterloo, B. C., Yao, S., Zhou, Y., Vona, B., Bishop, C., Bizaki-vallaskangas, A., Canlon, B., Castellana, F., Chasman, D. I., Cherny, S., Christensen, K., Concas, M. P., Correa, A., Elkon, R., Mengel-from, J., Gao, Y., ... Esko, T. (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. https://doi.org/10.1016/j.ajhg.2022.04.010

@article{dd8e3718ddc941e6993da9677b7213d1,

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

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.",

author = "Natalia Trpchevska and Freidin, {Maxim B.} and Linda Broer and Oosterloo, {Berthe C.} and Shuyang Yao and Yitian Zhou and Barbara Vona and Charles Bishop and Argyro Bizaki-vallaskangas and Barbara Canlon and Fabio Castellana and Chasman, {Daniel I.} and Stacey Cherny and Kaare Christensen and Concas, {Maria Pina} and Adolfo Correa and Ran Elkon and Jonas Mengel-from and Yan Gao and Giersch, {Anne B.s.} and Giorgia Girotto and Alexander Gudjonsson and Vilmundur Gudnason and Heard-costa, {Nancy L.} and Ronna Hertzano and Hjelmborg, {Jacob V.b.} and Jens Hjerling-leffler and Hoffman, {Howard J.} and Jaakko Kaprio and Johannes Kettunen and Kristi Krebs and K{\"a}hler, {Anna K.} and Francois Lallemend and Launer, {Lenore J.} and I-min Lee and Hampton Leonard and Chuan-ming Li and Hubert Lowenheim and Magnusson, {Patrik K.e.} and {Van Meurs}, Joyce and Lili Milani and Morton, {Cynthia C.} and Antti M{\"a}kitie and Nalls, {Mike A.} and Nardone, {Giuseppe Giovanni} and Marianne Nygaard and Teemu Palviainen and Sheila Pratt and Nicola Quaranta and Joel R{\"a}m{\"o} and Elmo Saarentaus and Rodolfo Sardone and Satizabal, {Claudia L.} and Schweinfurth, {John M.} and Sudha Seshadri and Eric Shiroma and Eldad Shulman and Eleanor Simonsick and Christopher Spankovich and Anke Tropitzsch and Lauschke, {Volker M.} and Sullivan, {Patrick F.} and Andre Goedegebure and Cederroth, {Christopher R.} and Williams, {Frances M.k.} and Nagtegaal, {Andries Paul} and Andres Metspalu and Mari Nelis and Reedik M{\"a}gi and T{\~o}nu Esko",

year = "2022",

month = may,

day = "16",

doi = "10.1016/j.ajhg.2022.04.010",

language = "English",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

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Trpchevska, N, Freidin, MB, Broer, L, Oosterloo, BC, Yao, S, Zhou, Y, Vona, B, Bishop, C, Bizaki-vallaskangas, A, Canlon, B, Castellana, F, Chasman, DI, Cherny, S, Christensen, K, Concas, MP, Correa, A, Elkon, R, Mengel-from, J, Gao, Y, Giersch, ABS, Girotto, G, Gudjonsson, A, Gudnason, V, Heard-costa, NL, Hertzano, R, Hjelmborg, JVB, Hjerling-leffler, J, Hoffman, HJ, Kaprio, J, Kettunen, J, Krebs, K, Kähler, AK, Lallemend, F, Launer, LJ, Lee, I, Leonard, H, Li, C, Lowenheim, H, Magnusson, PKE, Van Meurs, J, Milani, L, Morton, CC, Mäkitie, A, Nalls, MA, Nardone, GG, Nygaard, M, Palviainen, T, Pratt, S, Quaranta, N, Rämö, J, Saarentaus, E, Sardone, R, Satizabal, CL, Schweinfurth, JM, Seshadri, S, Shiroma, E, Shulman, E, Simonsick, E, Spankovich, C, Tropitzsch, A, Lauschke, VM, Sullivan, PF, Goedegebure, A, Cederroth, CR, Williams, FMK, Nagtegaal, AP, Metspalu, A, Nelis, M, Mägi, R & Esko, T 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. https://doi.org/10.1016/j.ajhg.2022.04.010

TY - JOUR

T1 - Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss

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 - 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 - Nardone, Giuseppe Giovanni

AU - Nygaard, Marianne

AU - Palviainen, Teemu

AU - Pratt, Sheila

AU - Quaranta, Nicola

AU - Rämö, Joel

AU - Saarentaus, Elmo

AU - Sardone, Rodolfo

AU - Satizabal, Claudia L.

AU - Schweinfurth, John M.

AU - Seshadri, Sudha

AU - Shiroma, Eric

AU - Shulman, Eldad

AU - Simonsick, Eleanor

AU - Spankovich, Christopher

AU - Tropitzsch, Anke

AU - Lauschke, Volker M.

AU - Sullivan, Patrick F.

AU - Goedegebure, Andre

AU - Cederroth, Christopher R.

AU - Williams, Frances M.k.

AU - Nagtegaal, Andries Paul

AU - Metspalu, Andres

AU - Nelis, Mari

AU - Mägi, Reedik

AU - Esko, Tõnu

PY - 2022/5/16

Y1 - 2022/5/16

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.

U2 - 10.1016/j.ajhg.2022.04.010

DO - 10.1016/j.ajhg.2022.04.010

M3 - Article

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

ER -

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

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