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.