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.

项目总结/文摘