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

Estonian Biobank Research Team, 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, Andres Metspalu, Mari NelisReedik Mägi, Tõnu Esko, 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

Tutkimustuotos: ArtikkeliScientificvertaisarvioitu

2 Lataukset (Pure)

Abstrakti

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.

AlkuperäiskieliEnglanti
Sivut1077-1091
Sivumäärä15
JulkaisuAmerican Journal of Human Genetics
Vuosikerta109
Numero6
DOI - pysyväislinkit
TilaJulkaistu - 2 kesäk. 2022
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Julkaisufoorumi-taso

  • Jufo-taso 3

!!ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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