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

Abstract

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 < 5 × 10^-8), ZNF185 (rs186256023, p = 4.9 × 10^-10) and MAP7D2 (rs4370706, p = 2.3 × 10^-8) in combined analysis of males and females, and LOC101928437 (rs138497700, p = 8.9 × 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.

Keywords: LOC101928437; MAP7D2; UK Biobank; X chromosome; ZNF185; age-related hearing loss.

FIGURE 1

Manhattan plots for the analysis of non-pseudo autosomal region of the X chromosome. The results are shown for the analysis of H-Both: males and females (purple); females only (green) and males only (blue). The y-axis displays −log₁₀ for each variant tested and the X-axis their position. The horizontal red and blue lines show the threshold for genome-wide significant (p = 5 × 10⁻⁸) and suggestive (p = 1 × 10⁻⁵) associations, respectively.