Environmental and genetic risk factors for tinnitus

Abstract

Tinnitus is a phantom auditory sensation, most often referred to as “ringing in the ears” with detrimental effect on quality of life. Between 4% and 37% of the global population has experienced tinnitus at some point in their life. For every 1 out of 10 individuals experiencing tinnitus, it becomes a severely impactful condition, affecting concentration, sleep, mood, and general quality of life. Despite its high prevalence and severe socio-economic burden, there is no successful treatment.

The work presented in this thesis uses multiple scientific approaches to better understand the etiology of tinnitus, with the emphasis on the genetic landscape in order to gain insight into its molecular origins.

First, we identify important gaps in knowledge on environmental risk factors associated with tinnitus. Second, we show using genetic epidemiology methods that severe tinnitus runs in families, which changes the current narrative that tinnitus would be generated purely due to environmental factors. Third, as tinnitus is commonly linked to hearing loss, we used a genome-wide biostatistical approach to reveal the genetic architecture of hearing loss, that will be further essential in distinguishing the two conditions. Fourth, we investigated the whole genome in relation to tinnitus to map correlated genomic regions and consequently, specific genes associated with tinnitus. Finally, we used a high-throughput sequencing of protein coding regions of the genome to identify disease-causing mutations impacting severe tinnitus.

The work presented in this thesis provides insights from multiple aspects into the origins of tinnitus and will serve as a backbone to understanding the pathophysiology of the disorder.