Tinnitus: Audiological measures and genetic susceptibility

耳鸣：听力学测量和遗传易感性

• 批准号: 10359459
• 负责人: Ishan Sunilkumar Bhatt
• 金额: $ 13.53万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10359459
• 关键词: Acute; Address; Adolescent; Age; Aging; American; Anxiety; Audiology; Auditory Evoked Potentials; Auditory Perception; Bioinformatics; Candidate Disease Gene; Characteristics; Chronic; Clinical; Complex; Confounding Factors (Epidemiology); Development; Disease; Doctor of Philosophy; Education; Environmental Exposure; Environmental Risk Factor; Ethnic Origin; Exhibits; Exposure to; Family; Financial compensation; Frequencies; General Population; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Risk; Genetic study; Genotype; Goals; Health; Health Personnel; Health Policy; Health Professional; Hearing; Hearing problem; Human; Hyperacusis; Impaired cognition; Individual; Industrial Arts; Investigation; Knowledge; Machine Learning; Measures; Mental Depression; Military Personnel; Modeling; Molecular; Multivariate Analysis; Music; Noise; Nucleotides; Otitis Media; PTGS1 gene; PTGS2 gene; Participant; Pharmaceutical Preparations; Phase; Phenotype; Physiological; Pilot Projects; Policy Maker; Population; Predisposition; Prevalence; Prevention strategy; Prostaglandin-Endoperoxide Synthase; Public Health; Quality of life; Regulation; Reporting; Research; Research Personnel; Risk; Risk Factors; Sampling; Serotonin; Silicon Dioxide; Sleeplessness; Smoking; Sodium; Source; Systemic disease; Testing; Tinnitus; United States Department of Veterans Affairs; Variant; Veterans; age related; aged; aging population; base; career; case control; causal variant; clinical development; college; experience; gene environment interaction; genetic association; genetic testing; genetic variant; genome wide association study; hearing impairment; individualized medicine; innovation; insight; knowledge base; learning strategy; novel; otoacoustic emission; preventive intervention; relating to nervous system; serotonin receptor; serotonin transporter; sound; statistics; teacher; trait; treatment strategy; voltage gated channel; young adult

PROJECT SUMMARY/ABSTRACT Tinnitus, the phantom perception of sound in absence of an external sound source, is a prevalent hearing disorder. To date, the exact neural and molecular mechanisms underlying tinnitus are not known. Tinnitus is associated with a number of otological diseases and clinical conditions; however, almost 50% of tinnitus cases are not attributable to any known cause (Stouffer & Tyler, 1990). There is likely a genetic component to tinnitus (Sand et al, 2007). A critical gap in the knowledge base is how to clinically identify those who are genetically predisposed to tinnitus well before they acquire this hearing health issue. The short-term goal of this R21 Early Career Research PAR 16-057 application, entitled “Tinnitus: Audiological measures and genetic susceptibility,” is to identify detailed phenotypic and genotypic profiles of chronic tinnitus in young adults. The application is proposed by a team of researchers: The PI is Ishan Bhatt, Ph.D. in audiology (CCC-A, FAAA), who is working with Co-PI’s Jason Wilder, Ph.D. in genetics, Jin Wang, Ph.D. in statistics, and Raquel Dias, Ph.D. in Bioinformatics. This project will fill the gap in knowledge by identifying the critical variables associated with a genetic predisposition to CT. This investigation will include college-aged young participants to control for age- related confounding variables such as systemic diseases and hearing loss. According to the PI’s pilot study (Bhatt, 2017a), the estimated prevalence of chronic tinnitus (CT), acute tinnitus (AT) and no tinnitus (NT) is around 8%, 13% and 79%, respectively. To accomplish our short-term goal, we will conduct a case-control- control exonic genome-wide association study (GWAS) (N = 300) in which subjects will be divided into three groups: those with (1) CT (tinnitus for > 1 year; n=100), (2) AT (tinnitus for ≤ 1 year, presumably due to acute environmental exposure; n=100); and (3) NT (no experience of tinnitus in a lifetime; n=100). The Specific Aims are: (1) to identify associations between exonic Single Nucleotide Polymorhisms (SNPs) and tinnitus phenotype. Based on the criteria laid out in the preliminary studies (Bhatt, 2017a; Bhatt et al., 2016; Phillip et al., 2015), our working hypothesis is that causal SNPs will exhibit a higher frequency of a specific genotype for subjects with CT compared to subjects with AT and NT. (2) To identify association between selected SNPs in a candidate set of genes and audiologic measures among subjects with CT, AT and NT, Based on our preliminary studies (Bhatt et al., 2016, Phillips et al., 2015), our working hypothesis is that subjects with causal alleles for CT will exhibit pathophysiological variation in the audiometric measures. Significance: Successful completion of this project will enable us to identify phenotypic and genotypic profiles of CT. This will help us to achieve our long term goal, which is to develop a genetic Risk Profile that can be used by health-care providers, and educators (e.g., health professionals, music and industrial arts teachers) to identify individuals genetically at risk for CT.

项目摘要/摘要 耳鸣是在没有外部声音的情况下对声音的幻影感知，是一种普遍的听力 紊乱。迄今为止，尚不清楚耳鸣的确切神经和分子机制。耳鸣是 与许多耳动疾病和临床疾病有关；但是，几乎50％的耳鸣病例 不是归因于任何已知原因（Stouffer＆Tyler，1990）。耳鸣可能有遗传成分 （Sand等，2007）。知识库中的一个关键差距是如何在临床上识别那些遗传的人 在获得此听力健康问题之前，他们会很容易对耳鸣。该R21早期的短期目标 职业研究PAR 16-057应用，标题为“耳鸣：听力学测量和遗传易感性”， 是为了确定年轻人慢性耳鸣的详细表型和基因型特征。该应用程序是 由研究人员团队提出的：PI是Ishan Bhatt博士。在工作的音频（CCC-A，FAAA）中 与Co-Pi的Jason Wilder博士一起在遗传学中，金·王（Jin Wang）博士在统计和拉奎尔·迪亚斯（Raquel Dias）博士学位上在 生物信息学。该项目将通过识别与某人相关的关键变量来填补差距 CT的遗传易感性。这项投资将包括大学年龄的年轻参与者以控制年龄 - 相关的混杂变量，例如全身性疾病和听力损失。根据PI的试点研究 （Bhatt，2017a），慢性耳鸣（CT），急性耳鸣（AT）和无耳鸣（NT）的估计患病率是 分别约为8％，13％和79％。为了实现我们的短期目标，我们将进行案件对照 - 控制外显子基因组关联研究（GWAS）（n = 300），其中受试者将被分为三个 组：（1）CT（耳鸣> 1年; n = 100），（2）at（Tinnitus≤1年）的组：大概是由于急性造成的 环境暴露； n = 100）; （3）nt（一生中没有耳鸣的经验； n = 100）。具体目标 为：（1）识别外显子单核苷酸多矩阵（SNP）和耳鸣之间的关联 表型。根据初步研究中列出的标准（Bhatt，2017a； Bhatt等，2016； Phillip et Al。，2015年），我们的工作假设是，因果SNP将表现出更高的特定基因型的频率 与AT和NT受试者相比，患有CT的受试者。 （2）识别A中选定的SNP之间的关联 根据我们 初步研究（Bhatt等，2016； Phillips等，2015），我们的工作假设是患有因果关系的受试者 CT等位基因在听力测量值中将存在病理生理变异。意义：成功 该项目的完成将使我们能够确定CT的表型和基因型谱。这将帮助我们 实现我们的长期目标，即开发遗传风险概况，可以由医疗保健使用 提供者和教育工作者（例如卫生专业人员，音乐和工业艺术老师）确定个人 遗传上有CT的风险。