Naderi Elnaz, Cornejo-Sanchez Diana M, Li Guangyou, Schrauwen Isabelle, Wang Gao T, Dewan Andrew T, Leal Suzanne M
Center for Statistical Genetics, Gertrude H. Sergievsky Center, and the Department of Neurology, Columbia University Medical Center, New York, NY, United States.
Department of Chronic Disease Epidemiology and Center for Perinatal, Pediatric and Environmental Epidemiology, Yale School of Public Health, New Haven, CT, United States.
Front Genet. 2023 Feb 21;14:1106328. doi: 10.3389/fgene.2023.1106328. eCollection 2023.
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), (rs186256023, = 4.9 × 10) and (rs4370706, = 2.3 × 10) in combined analysis of males and females, and (rs138497700, = 8.9 × 10) in the sex-stratified analysis of males. mRNA expression analysis showed and 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.
年龄相关性（AR）听力损失（HL）是最常见的感觉障碍，遗传度为55%。本研究的目的是通过分析从英国生物银行获得的数据，确定与ARHL相关的X染色体上的基因变异。我们对约460,000名欧洲白人自我报告的HL测量值与X染色体上的基因分型和推断变异进行了关联分析。在男性和女性的联合分析中，我们确定了三个与ARHL相关的位点，其全基因组显著性水平（p < 5 × 10），（rs186256023， = 4.9 × 10）和（rs4370706， = 2.3 × 10），在男性的性别分层分析中为（rs138497700， = 8.9 × 10）。mRNA表达分析表明 和 在小鼠和成人内耳组织中表达，特别是在内毛细胞中。我们估计X染色体上的变异仅解释了ARHL的少量变异，即0.4%。这项研究表明，尽管X染色体上可能有一些基因导致ARHL，但X染色体在ARHL病因学中所起的作用可能有限。
