The genetic contribution of the X chromosome in age-related hearing loss.
The genetic contribution of the X chromosome in age-related hearing loss.
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DOI：
10.3389/fgene.2023.1106328
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发表时间：
2023
影响因子：
3.7
通讯作者：
Leal, Suzanne M. M.
中科院分区：
文献类型：
--
作者：
Naderi, Elnaz;Cornejo-Sanchez, Diana M. M.;Li, Guangyou;Schrauwen, Isabelle;Wang, Gao T. T.;Dewan, Andrew T. T.;Leal, Suzanne M. M.
听力损失是最常见的感觉障碍，遗传率为55%。本研究的目的是通过分析从英国生物银行获得的数据，以确定与ARHL相关的X染色体上的遗传变异。我们对来自1460，000名欧洲白色人的自我报告的HL测量值与X染色体上的基因分型和插补变异之间进行了关联分析。我们确定了三个与ARHL相关的基因座，具有全基因组显著性水平。（p < 5 × 10−8），ZNF 185（rs186256023，p = 4.9 × 10−10）和MAP7D2（rs4370706，p = 2.3 × 10−8），以及LOC 101928437（rs138497700，p = 8.9 × 10−9）。计算机模拟mRNA表达分析表明，MAP7D2和ZNF 185在小鼠和成人内耳组织中表达，特别是在内毛细胞中。我们估计只有少量的ARHL变异，0.4%，是由X染色体上的变异解释的。这项研究表明，虽然可能有一些基因有助于ARHL的X染色体上，X染色体的作用，在ARHL的病因可能是有限的。
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.
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影响因子：
5
作者：
Fry A;Littlejohns TJ;Sudlow C;Doherty N;Adamska L;Sprosen T;Collins R;Allen NE
通讯作者：
Allen NE
影响因子：
4.4
作者：
Kikuchi K;Sakamoto Y;Uezu A;Yamamoto H;Ishiguro KI;Shimamura K;Saito T;Hisanaga SI;Nakanishi H
通讯作者：
Nakanishi H
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
16.6
作者：
Huang J;Howie B;McCarthy S;Memari Y;Walter K;Min JL;Danecek P;Malerba G;Trabetti E;Zheng HF;UK10K Consortium;Gambaro G;Richards JB;Durbin R;Timpson NJ;Marchini J;Soranzo N
通讯作者：
Soranzo N
影响因子：
4.8
作者：
Ponticorvo, Sara;Manara, Renzo;Esposito, Fabrizio
通讯作者：
Esposito, Fabrizio