AUTHOR=Naderi Elnaz , Cornejo-Sanchez Diana M. , Li Guangyou , Schrauwen Isabelle , Wang Gao T. , Dewan Andrew T. , Leal Suzanne M. 

TITLE=The genetic contribution of the X chromosome in age-related hearing loss

JOURNAL=Frontiers in Genetics

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1106328

DOI=10.3389/fgene.2023.1106328

ISSN=1664-8021

ABSTRACT=<p>Age-related (AR) hearing loss (HL) is the most common sensory impairment with heritability of 55%. The aim of this study was to identify genetic variants on chromosome X associated with ARHL through the analysis of data obtained from the UK Biobank. We performed association analysis between self-reported measures of HL and genotyped and imputed variants on chromosome X from ∼460,000 white Europeans. We identified three loci associated with ARHL with a genome-wide significance level (p &lt; 5 × 10<sup>−8</sup>), <italic>ZNF185</italic> (rs186256023, <italic>p</italic> = 4.9 × 10<sup>−10</sup>) and <italic>MAP7D2</italic> (rs4370706, <italic>p</italic> = 2.3 × 10<sup>−8</sup>) in combined analysis of males and females, and <italic>LOC101928437</italic> (rs138497700, <italic>p</italic> = 8.9 × 10<sup>−9</sup>) in the sex-stratified analysis of males. <italic>In-silico</italic> mRNA expression analysis showed <italic>MAP7D2</italic> and <italic>ZNF185</italic> are expressed in mice and adult human inner ear tissues, particularly in the inner hair cells. We estimated that only a small amount of variation of ARHL, 0.4%, is explained by variants on the X chromosome. This study suggests that although there are likely a few genes contributing to ARHL on the X chromosome, the role that the X chromosome plays in the etiology of ARHL may be limited.</p>