Sunday, June 26, 2022

Researchers Identify Ten New Hearing Loss Genes | Sci-News.com

A multinational team of scientists has performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant genes, 10 of which are new to science. Their results cast doubt on the understanding that age-related hearing impairment originates mainly from sensory hair cells. They argue that the stria vascularis, a part of the cochlea in the ear, is a new target for treatments to help people with hearing loss.

trpchevska et al, identified 48 associated loci, including 10 novel associations and 8 missense SNPs; the work highlights the role of the cochlear lateral wall including the stria vascularis and the outer sulcus as a contributor to hearing loss; the results provide a valuable resource for the selection of promising genes for further functional validation in pre-clinical models and define targets for screening purposes, drug development, gene therapy, or stratification approaches. Image credit: Pexels.

The number of people with mild-to-complete hearing impairment is projected to increase to an estimated 2.45 billion worldwide by 2050, principally driven by age-related hearing impairment.

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Hearing impairment is ranked third for causes of global years lived with disability across all ages and the leading cause in those older than 70, as compared with all other disease categories.

The overall global cost of unaddressed hearing loss exceeds $981 billion annually.

Age-related hearing impairment has been associated with social withdrawal, depression, anxiety, as well as cognitive decline and dementia.

There is no preventive treatment for hearing decline and therapeutics are currently available only in the form of hearing aids or cochlear implants.

Moreover, the impact of untreated hearing loss remains underestimated as governmental and industry incentives are still very low in comparison to other diseases of equal prevalence.

Evaluation of enrichment of common-variant hearing loss genome-wide association study results in scRNA-seq mouse datasets.  Image credit: Trpchevska et al., doi: 10.1016/j.ajhg.2022.04.010.

Evaluation of enrichment of common-variant hearing loss genome-wide association study results in scRNA-seq mouse datasets. Image credit: Trpchevska et al., doi: 10.1016/j.ajhg.2022.04.010.

In order to gain fundamental knowledge on the genetic basis of hearing loss, King’s College London Professor Frances Williams and colleagues conducted a meta-analysis of 17 hearing loss genome-wide association studies using both ICD diagnoses and self-reported hearing loss.

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The study comprised 147,997 affected individuals and 575,269 control subjects including 60,941 affected individuals that were not in the team’s previously published meta-analysis.

The researchers identified 48 genes linked to hearing loss, including 10 new variants newly linked to hearing.

Further analysis looking at mouse genetics indicated that age-related hearing loss is due to changes in the stria vascularis which is necessary for hearing.

The results provide targets for the basis of future research which could improve therapies against hearing loss.

“Our findings identify 10 genes newly linked with hearing loss,” Professor Williams said.

“This study points to genes we could target for screening purposes, drug development and even gene therapy in the future.”

“The study provides a solid foundation for ultimately improving therapies against hearing loss.”

“It was hypothesized since the 1970s that the stria vascularis may play a role in hearing loss in humans, but the molecular evidence for this was missing until today,” added Karolinska Institute’s Dr. Christopher R. Cederroth.

The results were published in the American Journal of Human Genetics,

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Natalia Trpchevska et al, Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss. AJHG, published online May 16, 2022; doi: 10.1016/j.ajhg.2022.04.010

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