Genome-wide association meta-analysis identifies five novel loci for age-related hearing impairment
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Published:2019-10-23
Issue:1
Volume:9
Page:
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ISSN:2045-2322
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Container-title:Scientific Reports
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language:en
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Short-container-title:Sci Rep
Author:
Nagtegaal Andries PaulORCID, Broer Linda, Zilhao Nuno R., Jakobsdottir Johanna, Bishop Charles E., Brumat Marco, Christiansen Mark W., Cocca MassimilianoORCID, Gao Yan, Heard-Costa Nancy L.ORCID, Evans Daniel S., Pankratz Nathan, Pratt Sheila R., Price T. Ryan, Spankovich Christopher, Stimson Mary R., Valle Karen, Vuckovic Dragana, Wells Helena, Eiriksdottir Gudny, Fransen Erik, Ikram Mohammad ArfanORCID, Li Chuang-Ming, Longstreth W. T., Steves Claire, Van Camp Guy, Correa AdolfoORCID, Cruickshanks Karen J., Gasparini Paolo, Girotto GiorgiaORCID, Kaplan Robert C., Nalls Michael, Schweinfurth John M., Seshadri Sudha, Sotoodehnia Nona, Tranah Gregory J., Uitterlinden André G.ORCID, Wilson James G., Gudnason VilmundurORCID, Hoffman Howard J., Williams Frances M. K., Goedegebure André
Abstract
AbstractPrevious 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 theILDR1gene 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.
Funder
Action on Hearing Loss Chronic Disease Research Foundation U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders
Publisher
Springer Science and Business Media LLC
Subject
Multidisciplinary
Reference65 articles.
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