Making a difference - genetic research into cause and risk of deafness

Multidisciplinary research led by UCLH BRC is advancing understanding of the genetics of deafness (Otogenetics) and accelerating the translation of new knowledge to improve diagnostics and patient care.

The auditory system, that allows us to hear, is one of the most complex and highly specialised organs in the human body. Each of its different components are critical for hearing. Hundreds of different genes and mutations causing deafness have been identified to date.

A world-leading team of researchers at UCLH BRC have recently discovered 44 new genes involved in age-related hearing loss (1), and through collaboration with BRC biomedical engineers, have identified shared genetic vulnerability for hearing loss and dementia. As a result, the team has created a preliminary polygenic risk score (2) which could be used to predict those at risk of hearing loss.

Despite these rapid advances, many families with inherited deafness are still unable to get a genetic diagnosis and face uncertainties about their prognosis and chance of passing deafness on to their children. This lack of interpretation of genetic tests also means trials of novel targeted molecular and genetic treatments lack precision because participants are not precisely genotyped.

To accelerate the translation of the research into patient benefit, the UCLH BRC team have established national collaborations and initiatives. They have developed national infrastructure to deliver hearing projects at scale including the NIHR Hearing Health Informatics Collaborative, the NIHR Hearing Health Translational

 Research Collaborative and Polygenic Risk Scores in Dementia initiatives.

The team has also established a unique transdisciplinary Otogenetics service and registry, bringing together world-leading researchers in human and mouse hearing genetics with clinicians treating families with deafness at our Royal National Ear Nose and Throat Hospital and the Great Ormond Street Hospital.

This allows the team to review undiagnosed families with deafness recruited to the 100,000 Genomes project to validate new genes and make comparisons between new data from UK Biobank Study and the International Mouse Phenotyping Consortium (3).

The unique Otogenetics service provides a standardised pathway from consultation to treatment, integrating research with the latest patient diagnostics and care and offering families opportunities to take part in upcoming trials of innovative targeted treatments.

1. Wells HRR et al. Am J Hum Genet. 2019; 2. Abidin et al. npj Aging Mech Dis. 2021; 3. Bowl, M.R. et al. Nat Commun. 2017