Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, SE1 7EH, UK.
UCL Ear Institute, University College London, London, WC1X 8EE, UK.
Sci Rep. 2021 Mar 19;11(1):6470. doi: 10.1038/s41598-021-85871-6.
Tinnitus is a prevalent condition in which perception of sound occurs without an external stimulus. It is often associated with pre-existing hearing loss or noise-induced damage to the auditory system. In some individuals it occurs frequently or even continuously and leads to considerable distress and difficulty sleeping. There is little knowledge of the molecular mechanisms involved in tinnitus which has hindered the development of treatments. Evidence suggests that tinnitus has a heritable component although previous genetic studies have not established specific risk factors. From a total of 172,608 UK Biobank participants who answered questions on tinnitus we performed a case-control genome-wide association study for self-reported tinnitus. Final sample size used in association analysis was N = 91,424. Three variants in close proximity to the RCOR1 gene reached genome wide significance: rs4906228 (p = 1.7E-08), rs4900545 (p = 1.8E-08) and 14:103042287_CT_C (p = 3.50E-08). RCOR1 encodes REST Corepressor 1, a component of a co-repressor complex involved in repressing neuronal gene expression in non-neuronal cells. Eleven other independent genetic loci reached a suggestive significance threshold of p < 1E-06.
耳鸣是一种常见的病症，其特征是感知到声音而没有外部刺激。它通常与先前存在的听力损失或噪声引起的听觉系统损伤有关。在某些人中，它经常发生甚至持续存在，导致相当大的痛苦和睡眠困难。对于涉及耳鸣的分子机制知之甚少，这阻碍了治疗方法的发展。有证据表明耳鸣具有遗传成分，尽管先前的遗传研究尚未确定具体的风险因素。我们从总共回答了耳鸣问题的 172608 名英国生物库参与者中，对自我报告的耳鸣进行了病例对照全基因组关联研究。关联分析中最终使用的样本量为 N=91424。RCOR1 基因附近的三个变体接近全基因组显著水平：rs4906228（p=1.7E-08），rs4900545（p=1.8E-08）和 14:103042287_CT_C（p=3.50E-08）。RCOR1 编码 REST 核心抑制因子 1，是一种抑制神经元基因表达的共抑制复合物的组成部分。其他 11 个独立的遗传位点达到了 p<1E-06 的提示显著阈值。
