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.

Highlights

  • Tinnitus, the perception of a phantom sound, affects nearly 15% of the population

  • Genetic studies would help in identifying diagnostic markers for subgroups of tinnitus patients or markers of resistance to treatment in order to improve the selection of subjects and optimize treatment outcome

  • We propose different approaches toward the genetic elucidation of tinnitus including the analysis of concordance in twins, familial aggregation studies, exome sequencing in families with multiple cases, and sequencing studies in cohorts of patients with extreme phenotypes

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Summary

INTRODUCTION

The perception of a phantom sound, affects nearly 15% of the population. It can severely affect quality of life in 3–6% of the population, becoming chronically bothersome, and incapacitating (Davis and Refaie, 2000). Pawelczyk et al (2012) conducted a case-control study in Poland including 626 subjects exposed to occupational noise (128 with tinnitus and 498 without tinnitus) While they reported an association with the SNP rs915539 in normal hearing subjects (p = 0.005), no ancestry-informative markers were used and the current standards in genetic association studies require a replication in another association study with an independent population, something that to our knowledge has not been yet reported.

Methods
Findings
Design of Tinnitus Sequencing Studies
Full Text
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