Approved research

Exploring the genetic architecture of age-related hearing impairment

Lay summary

Hearing loss is the fourth leading cause of disability globally and leads to social isolation, and reduced quality of life. Adult hearing loss has been associated with lower economic success, increased rates of dementia, hospitalization, and even death. The current standard of care for adult patients suffering from progressive hearing loss is monitoring with serial audiograms, hearing aids, and eventually cochlear implants if required. Although hearing aids and cochlear implants allow patients with even profound hearing loss to understand speech, they do not provide 'normal' hearing and patients continue to have difficulty in background noise, talking on the phone, and listening to music. Even if suspected of harboring a genetic mutation responsible for their hearing loss, few undergo genetic testing largely due to the perception that there is unlikely to be prognostic information available and there are currently no therapeutic options. Our goal is to change this (mis)impression. Treatment options directed at the specific causative genetic mutation, applied early in the course of the disease, could avoid decades of hearing rehabilitation and maintain patient quality of life. Further, early identification and intervention has the potential to prevent irreversible damage to the complex anatomic relationships necessary for proper cochlear function. Tens of thousands of patients obtain hearing aids each year and thousands more move on to cochlear implantation. The vast majority never have a cause for their hearing loss determined and their providers have no alternative therapies to offer. Further, those with severe or rapidly progressive hearing loss often undergo extensive and expensive testing and may be treated empirically with steroids exposing them to potentially serious side effects. Too often these diagnostic investigations return no answers and treatment trials fail to halt or reverse their loss. The inner ear provides a unique opportunity for genetic intervention. It is accessible with minimal morbidity, has anatomic boundaries that limit spread of therapeutic vectors to surrounding tissues, and can provide reliable and objective outcome measures. These interventions are not possible however, without a fundamental knowledge of the underlying mutations and understanding of the natural history of specific genetic changes. We aim to exploit data in the UK Biobank to determine the genetic architecture of hearing loss in adult populations.