TY - JOUR
T1 - Genome-wide association meta-analysis identifies five novel loci for age-related hearing impairment
AU - Nagtegaal, Andries Paul
AU - Broer, Linda
AU - Zilhao, Nuno R.
AU - Jakobsdottir, Johanna
AU - Bishop, Charles E.
AU - Brumat, Marco
AU - Christiansen, Mark W.
AU - Cocca, Massimiliano
AU - Gao, Yan
AU - Heard-Costa, Nancy L.
AU - Evans, Daniel S.
AU - Pankratz, Nathan
AU - Pratt, Sheila R.
AU - Price, T. Ryan
AU - Spankovich, Christopher
AU - Stimson, Mary R.
AU - Valle, Karen
AU - Vuckovic, Dragana
AU - Wells, Helena
AU - Eiriksdottir, Gudny
AU - Fransen, Erik
AU - Ikram, Mohammad Arfan
AU - Li, Chuang Ming
AU - Longstreth, W. T.
AU - Steves, Claire
AU - Van Camp, Guy
AU - Correa, Adolfo
AU - Cruickshanks, Karen J.
AU - Gasparini, Paolo
AU - Girotto, Giorgia
AU - Kaplan, Robert C.
AU - Nalls, Michael
AU - Schweinfurth, John M.
AU - Seshadri, Sudha
AU - Sotoodehnia, Nona
AU - Tranah, Gregory J.
AU - Uitterlinden, André G.
AU - Wilson, James G.
AU - Gudnason, Vilmundur
AU - Hoffman, Howard J.
AU - Williams, Frances M.K.
AU - Goedegebure, André
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-019-51630-x
DO - 10.1038/s41598-019-51630-x
M3 - Article
C2 - 31645637
AN - SCOPUS:85074063270
SN - 2045-2322
VL - 9
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 15192
ER -