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Abstract：
OBJECTIVE: To assess the available evidence to support a genetic contribution and define the role of common and rare variants in tinnitus.
METHODS: After a systematic search and quality assessment, 31 records including 383,063 patients were selected (14 epidemiological studies and 17 genetic association studies). General information on the sample size, age, sex, tinnitus prevalence, severe tinnitus distribution, and sensorineural hearing loss was retrieved. Studies that did not include data on hearing assessment were excluded. Relative frequencies were used for qualitative variables to compare different studies and to obtain average values. Genetic variants and genes were listed and clustered according to their potential role in tinnitus development.
RESULTS: The average prevalence of tinnitus estimated from population-based studies was 26.3% for any tinnitus, and 20% of patients with tinnitus reported it as an annoying symptom. One study has reported population-specific differences in the prevalence of tinnitus, the white ancestry being the population with a higher prevalence. Genome-wide association studies have identified and replicated two common variants in the Chinese population (rs2846071; rs4149577) in the intron of TNFRSF1A, associated with noise-induced tinnitus. Moreover, gene burden analyses in sequencing data from Spanish and Swede patients with severe tinnitus have identified and replicated ANK2, AKAP9, and TSC2 genes.
CONCLUSIONS: The genetic contribution to tinnitus is starting to be revealed and it shows population-specific effects in European and Asian populations. The common allelic variants associated with tinnitus that showed replication are associated with noise-induced tinnitus. Although severe tinnitus has been associated with rare variants with large effect, their role on hearing or hyperacusis has not been established.
METHODS: After a systematic search and quality assessment, 31 records including 383,063 patients were selected (14 epidemiological studies and 17 genetic association studies). General information on the sample size, age, sex, tinnitus prevalence, severe tinnitus distribution, and sensorineural hearing loss was retrieved. Studies that did not include data on hearing assessment were excluded. Relative frequencies were used for qualitative variables to compare different studies and to obtain average values. Genetic variants and genes were listed and clustered according to their potential role in tinnitus development.
RESULTS: The average prevalence of tinnitus estimated from population-based studies was 26.3% for any tinnitus, and 20% of patients with tinnitus reported it as an annoying symptom. One study has reported population-specific differences in the prevalence of tinnitus, the white ancestry being the population with a higher prevalence. Genome-wide association studies have identified and replicated two common variants in the Chinese population (rs2846071; rs4149577) in the intron of TNFRSF1A, associated with noise-induced tinnitus. Moreover, gene burden analyses in sequencing data from Spanish and Swede patients with severe tinnitus have identified and replicated ANK2, AKAP9, and TSC2 genes.
CONCLUSIONS: The genetic contribution to tinnitus is starting to be revealed and it shows population-specific effects in European and Asian populations. The common allelic variants associated with tinnitus that showed replication are associated with noise-induced tinnitus. Although severe tinnitus has been associated with rare variants with large effect, their role on hearing or hyperacusis has not been established.
摘要：
目的：评估支持遗传贡献的现有证据，并确定常见和罕见变异在耳鸣中的作用。
方法：经过系统的搜索和质量评估，选择了31条记录，包括383,063名患者（14项流行病学研究和17项遗传关联研究）。关于样本量的一般信息，年龄,性别,耳鸣患病率,严重的耳鸣分布，并恢复了感觉神经性听力损失。不包括听力评估数据的研究被排除在外。相对频率用于定性变量，以比较不同的研究并获得平均值。根据其在耳鸣发展中的潜在作用列出遗传变异和基因并进行聚类。
结果：根据人群研究估计的耳鸣平均患病率为26.3%，20％的耳鸣患者将其报告为令人讨厌的症状。一项研究报告了耳鸣患病率的人群特异性差异，白人祖先是患病率较高的人群。全基因组关联研究已经确定并复制了中国人群中TNFRSF1A内含子中的两个常见变体（rs2846071;rs4149577），与噪声引起的耳鸣有关。此外，西班牙和瑞典人重度耳鸣患者测序数据中的基因负荷分析鉴定并复制了ANK2,AKAP9和TSC2基因.
结论：耳鸣的遗传贡献开始被揭示，它显示了欧洲和亚洲人群的群体特异性效应。与显示复制的耳鸣相关的常见等位基因变体与噪声诱导的耳鸣相关。尽管严重的耳鸣与罕见的变异有很大的影响，他们对听力或听力亢进的作用尚未确定。
方法：经过系统的搜索和质量评估，选择了31条记录，包括383,063名患者（14项流行病学研究和17项遗传关联研究）。关于样本量的一般信息，年龄,性别,耳鸣患病率,严重的耳鸣分布，并恢复了感觉神经性听力损失。不包括听力评估数据的研究被排除在外。相对频率用于定性变量，以比较不同的研究并获得平均值。根据其在耳鸣发展中的潜在作用列出遗传变异和基因并进行聚类。
结果：根据人群研究估计的耳鸣平均患病率为26.3%，20％的耳鸣患者将其报告为令人讨厌的症状。一项研究报告了耳鸣患病率的人群特异性差异，白人祖先是患病率较高的人群。全基因组关联研究已经确定并复制了中国人群中TNFRSF1A内含子中的两个常见变体（rs2846071;rs4149577），与噪声引起的耳鸣有关。此外，西班牙和瑞典人重度耳鸣患者测序数据中的基因负荷分析鉴定并复制了ANK2,AKAP9和TSC2基因.
结论：耳鸣的遗传贡献开始被揭示，它显示了欧洲和亚洲人群的群体特异性效应。与显示复制的耳鸣相关的常见等位基因变体与噪声诱导的耳鸣相关。尽管严重的耳鸣与罕见的变异有很大的影响，他们对听力或听力亢进的作用尚未确定。
