Genome-wide association meta-analysis identifies five novel loci for age-related hearing impairment

Andries Paul Nagtegaal, Linda Broer, Nuno R. Zilhao, Johanna Jakobsdottir, Charles E. Bishop, Marco Brumat, Mark W. Christiansen, Massimiliano Cocca, Yan Gao, Nancy L. Heard-Costa, Daniel S. Evans, Nathan Pankratz, Sheila R. Pratt, T. Ryan Price, Christopher Spankovich, Mary R. Stimson, Karen Valle, Dragana Vuckovic, Helena Wells, Gudny EiriksdottirErik Fransen, Mohammad Arfan Ikram, Chuang Ming Li, W. T. Longstreth, Claire Steves, Guy Van Camp, Adolfo Correa, Karen J. Cruickshanks, Paolo Gasparini, Giorgia Girotto, Robert C. Kaplan, Michael Nalls, John M. Schweinfurth, Sudha Seshadri, Nona Sotoodehnia, Gregory J. Tranah, André G. Uitterlinden, James G. Wilson, Vilmundur Gudnason, Howard J. Hoffman, Frances M.K. Williams, André Goedegebure

Research output: Contribution to journalArticle

Abstract

Previous research has shown that genes play a substantial role in determining a person’s susceptibility to age-related hearing impairment. The existing studies on this subject have different results, which may be caused by difficulties in determining the phenotype or the limited number of participants involved. Here, we have gathered the largest sample to date (discovery n = 9,675; replication n = 10,963; validation n = 356,141), and examined phenotypes that represented low/mid and high frequency hearing loss on the pure tone audiogram. We identified 7 loci that were either replicated and/or validated, of which 5 loci are novel in hearing. Especially the ILDR1 gene is a high profile candidate, as it contains our top SNP, is a known hearing loss gene, has been linked to age-related hearing impairment before, and in addition is preferentially expressed within hair cells of the inner ear. By verifying all previously published SNPs, we can present a paper that combines all new and existing findings to date, giving a complete overview of the genetic architecture of age-related hearing impairment. This is of importance as age-related hearing impairment is highly prevalent in our ageing society and represents a large socio-economic burden.

Original languageEnglish (US)
Article number15192
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

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    Nagtegaal, A. P., Broer, L., Zilhao, N. R., Jakobsdottir, J., Bishop, C. E., Brumat, M., Christiansen, M. W., Cocca, M., Gao, Y., Heard-Costa, N. L., Evans, D. S., Pankratz, N., Pratt, S. R., Price, T. R., Spankovich, C., Stimson, M. R., Valle, K., Vuckovic, D., Wells, H., ... Goedegebure, A. (2019). Genome-wide association meta-analysis identifies five novel loci for age-related hearing impairment. Scientific reports, 9(1), [15192]. https://doi.org/10.1038/s41598-019-51630-x