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

Cruickshanks Lab // Publications // Oct 23 2019

PubMed ID: 31645637

Author(s): Nagtegaal AP, Broer L, Zilhao NR, Jakobsdottir J, Bishop CE, Brumat M, Christiansen MW, Cocca M, Gao Y, Heard-Costa NL, Evans DS, Pankratz N, Pratt SR, Price TR, Spankovich C, Stimson MR, Valle K, Vuckovic D, Wells H, Eiriksdottir G, Fransen E, Ikram MA, Li CM, Longstreth WT Jr, Steves C, Van Camp G, Correa A, Cruickshanks KJ, Gasparini P, Girotto G, Kaplan RC, Nalls M, Schweinfurth JM, Seshadri S, Sotoodehnia N, Tranah GJ, Uitterlinden AG, Wilson JG, Gudnason V, Hoffman HJ, Williams FMK, Goedegebure A. Genome-wide association meta-analysis identifies five novel loci for age-related hearing impairment. Sci Rep. 2019 Oct 23;9(1):15192. doi: 10.1038/s41598-019-51630-x. PMID 31645637

Journal: Scientific Reports, Volume 9, Issue 1, 10 2019

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.