Genetics of Tinnitus: An Emerging Area for Molecular Diagnosis and Drug Development

Abstract

Subjective tinnitus is the perception of sound in the absence of external or bodily-generated sounds. Chronic tinnitus is a highly prevalent condition affecting over 70 million people in Europe. A wide variety of comorbidities, including hearing loss, psychiatric disorders, neurodegenerative disorders, and temporomandibular joint (TMJ) dysfunction, have been suggested to contribute to the onset or progression of tinnitus; however, the precise molecular mechanisms of tinnitus are not well understood and the contribution of genetic and epigenetic factors remains unknown. Human genetic studies could enable the identification of novel molecular therapeutic targets, possibly leading to the development of novel pharmaceutical therapeutics. In this article, we briefly discuss the available evidence for a role of genetics in tinnitus and consider potential hurdles in designing genetic studies for tinnitus. Since multiple diseases have tinnitus as a symptom and the supporting genetic evidence is sparse, we propose various strategies to investigate the genetic underpinnings of tinnitus, first by showing evidence of heritability using concordance studies in twins, and second by improving patient selection according to phenotype and/or etiology in order to control potential biases and optimize genetic data output. The increased knowledge resulting from this endeavor could ultimately improve the drug development process and lead to the preventive or curative treatment of tinnitus.

The Effect of Antioxidant Supplementation in Patients with Tinnitus and Normal Hearing or Hearing Loss: A Randomized, Double-Blind, Placebo Controlled Trial

“…Despite the interesting results of this study and the advantage of being randomized and double-blinded, it has some limitations, including the enrollment of patients with high levels of oxidative stress (e.g., smokers, diabetics, elderly), the presence of compounds other than antioxidants in the supplement used and the heterogeneity of participants as far as tinnitus duration and severity, hearing loss, family history and age of tinnitus onset are concerned, shown to influence the response to treatment [71,72]. However, these limitations are compensated by the tight control of participants to ensure their compliance with the protocol, as well as the long follow-up and the adequate sample size of the study.…”

Tinnitus Is Associated with a Higher Risk of Benign Brain Tumors: A Nationwide, Population-Based Secondary Cohort Study of Young and Middle-Aged Adults

“…Tinnitus could be an early indicator for the occurrence of brain tumors in humans. Nevertheless, because of the lack of clinical information on the subtypes of tinnitus in the NHIRD, additional clinical and genetic studies are required to elucidate which subtypes of tinnitus are implicated in the pathogenesis of brain tumors [18-20]. …”

Tinnitus in Adults, a Health Problem: Implications for the Society and the Scientific Community

“…WG4 have published an updating study exposing that the available evidence for genetics in tinnitus is scarce and addressing the ideal design of studies concerning tinnitus genetic should use concordance twin studies and optimize patient selection according to phenotype and/or etiology to avoid genetic interpretation bias. 41 WG5 have gathered the opinions of many different stakeholders including people with tinnitus as well as professionals using consensus methods to produce recommendations for what tinnitus-related complaints are critical and important to measure when assessing treatment-related benefit. Of interest, these guidelines separately consider sound-based, psychology-based and pharmacology-based interventions, since each of these approaches has a different therapeutic rationale and therefore aims to address different tinnitus symptoms.…”