Tinnitus: Audiological measures and genetic susceptibility

耳鸣：听力学测量和遗传易感性

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要耳鸣是在没有外部声源的情况下对声音的幻觉，是一种常见的听力问题迄今为止，耳鸣的确切神经和分子机制尚不清楚。然而，近 50% 的耳鸣病例与多种耳科疾病和临床状况有关；无法归因于任何已知原因（Stouffer & Tyler，1990）。耳鸣可能与遗传因素有关。（Sand et al, 2007）知识库中的一个关键缺口是如何在临床上识别那些患有遗传性疾病的人。在出现听力健康问题之前就容易出现耳鸣 R21 Early 的短期目标。职业研究 PAR 16-057 申请，标题为“耳鸣：听力学测量和遗传易感性” 旨在确定年轻人慢性耳鸣的详细表型和基因型特征。由一组研究人员提出：PI 是听力学博士（CCC-A、FAAA），他正在联合首席研究员 Jason Wilder 是遗传学博士，Jin Wang 是统计学博士，Raquel Dias 是统计学博士。该项目将通过识别与生物信息学相关的关键变量来填补知识空白。 CT 的遗传易感性这项调查将包括大学年龄的年轻参与者，以控制年龄- 根据 PI 的试点研究，系统性疾病和听力损失等相关混杂变量。（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，我们将进行病例对照-。对照外显子全基因组关联研究 (GWAS) (N = 300)，其中受试者将被分为三组：（1）CT（耳鸣> 1年；n = 100），（2）AT（耳鸣≤1年，可能是由于急性环境暴露；n=100）；和（3）NT（一生中没有耳鸣经历；n=100）。是：(1) 确定外显子单核苷酸多态性 (SNP) 与耳鸣之间的关联基于初步研究中规定的标准（Bhatt，2017a；Bhatt 等人，2016；Phillip 等人） al., 2015)，我们的工作假设是，因果 SNP 将表现出更高频率的特定基因型 CT 受试者与 AT 和 NT 受试者进行比较 (2) 确定选定 SNP 之间的关联。 CT、AT 和 NT 受试者的候选基因和听力学测量数据集，基于我们的初步研究（Bhatt et al., 2016, Phillips et al., 2015），我们的工作假设是，具有因果关系的受试者 CT 的等位基因将在听力测量中表现出病理生理变化。该项目的完成将使我们能够鉴定 CT 的表型和基因型概况，这将有助于我们实现我们的长期目标，即开发可供医疗保健使用的遗传风险概况提供者和教育工作者（例如卫生专业人员、音乐和工业艺术教师）识别个人有 CT 遗传风险。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Influence of tinnitus, lifetime noise exposure, and firearm use on hearing thresholds, distortion product otoacoustic emissions, and their relative metric.

耳鸣、终生噪声暴露和枪支使用对听力阈值、失真产物耳声发射及其相对指标的影响。

DOI：
10.1121/10.0019880
发表时间：
2023-07-01
期刊：
The Journal of the Acoustical Society of America
影响因子：
0
作者：
I. Bhatt;J. Lichtenhan;R. Tyler;S. Goodman
通讯作者：
S. Goodman

AudioChip: A Deep Phenotyping Approach for Deconstructing and Quantifying Audiological Phenotypes of Self-Reported Speech Perception Difficulties.

AudioChip：一种深度表型分析方法，用于解构和量化自我报告的言语感知困难的听力表型。

DOI：
发表时间：
2022
期刊：
影响因子：
3.7
作者：
Bhatt, Ishan Sunilkumar;Dias, Raquel;Wineinger, Nathan;Pratt, Sheila;Wang, Jin;Washnik, Nilesh;Guthrie, O'neil;Wilder, Jason;Torkamani, Ali
通讯作者：
Torkamani, Ali

Association Analysis of Candidate Gene Polymorphisms and Audiometric Measures of Noise-Induced Hearing Loss in Young Musicians.

年轻音乐家噪声性听力损失候选基因多态性与听力测量的关联分析。

DOI：
10.1097/mao.0000000000002615
发表时间：
2020-03-13
期刊：
Otology & Neurotology
影响因子：
2.1
作者：
I. Bhatt;Raquel Dias;Nilesh J. Washnik;Jin Wang;O. Guthrie;M. Skelton;J. Lane;J. Wilder
通讯作者：
J. Wilder

Evaluation of cochlear activity in normal-hearing musicians.

正常听力音乐家的耳蜗活动评估。