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

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 & SIM;460,000 white Europeans. We identified three loci associated with ARHL with a genome-wide significance level (p < 5 x 10(-8)), ZNF185 (rs186256023, p = 4.9 x 10(-10)) and MAP7D2 (rs4370706, p = 2.3 x 10(-8)) in combined analysis of males and females, and LOC101928437 (rs138497700, p = 8.9 x 10(-9)) in the sex-stratified analysis of males. In-silico mRNA expression analysis showed MAP7D2 and ZNF185 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.

Automated summary

This study identified genetic variants on the X chromosome associated with age-related hearing loss (ARHL) through data analysis from the UK Biobank. Three loci were found to be significantly associated with ARHL, with two loci showing significance in both males and females and one locus showing significance in males only. The study suggests that the contribution of the X chromosome to the etiology of ARHL may be limited.