Cell types responsible for hearing loss in humans identified
Using gene expression data from different cell types in the inner ear and brain, researchers have been able to identify the cell types that mainly contribute to hearing loss. The findings confirm that hearing loss does not derive from the brain but from a distinct compartment in the cochlea, called the stria vascularis, which is the “powerhouse” of the inner ear. The study has been published in the American Journal of Human Genetics.
Recent global estimates reveal that more than 2.4 billion individuals will suffer from hearing loss by 2050. Genetic studies have linked several genes to hearing loss, each contributing to a small part of the risk of developing the disorder. It has been hypothesised since the 1970s that the stria vascularis may play a role in hearing loss in humans, but the molecular evidence for this has been missing.
“The findings in this study are important because they point to where research should be geared to provide better rehabilitation strategies for people with hearing loss. Researchers have mainly focused their efforts on the sensory hair cells, or the auditory neurons within the ear, with attempts to restore their function or to regenerate the missing cells. However, this may not prove useful if the powerhouse of the ear is dysfunctional,” says co-main author Christopher R. Cederroth, associate professor at the Department of Physiology and Pharmacology at Karolinska Institutet.
The study relied on collaborations between multiple centres and biobanks from Europe and the United States to gather human genetic data, which was then combined with a very large set of cellular data originating from mouse studies. Karolinska Institutet was a lead coordinating institution together with King’s College London and Erasmus MC.
“Many of the genes that were identified in humans have already been validated in mice, which shows the high translational validity of these animal models. This was crucial since it is very difficult to access human inner ear samples,” says Christopher Cederroth. “Now that we know which structure we should focus our research on, future steps will be to address how innovative therapeutic approaches can be used to target it and improve its function, in particular in individuals with age-related hearing loss.”
Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss
Trpchevska N, Freidin M B, Broer L, Oosterloo B C, Yao S, Zhou Y, Vona B, Bishop C, Bizaki-Vallaskangas A, Canlon B, Castellana F, Chasman D I, Cherny S, Christensen K, Pina Concas M, Correa A, Elkon R, Estonian Biobank Research Team, Mengel-From J, Gao Y, B.S. Giersch A, Girotto G, Gudjonsson A, Gudnason V, Heard-Costa N L, Hertzano R, v.B. Hjelmborg J, Hjerling-Leffler J, Hoffman H J, Kaprio J, Kettunen J, Krebs K, Kähler A K, Lallemend F, Launer L J, Lee I M, Leonard H, Li C M, Lowenheim H, K.E. Magnusson P, van Meurs J , Milani L, Morton C C, Mäkitie A, Nalls M A, Nardone G G, Nygaard M, Palviainen T, Pratt S, Quaranta N, Rämö J, Saarentaus E, Sardone R, Satizabal Barrera C L, Schweinfurth J M, Seshadri S H, Shiroma E, Shulman E, Simonsick E, Spankovich C, Tropitzsch A, Lauschke V M, Sullivan P F, Goedegebure A E, Cederroth C R, Williams F M K, Nagtegaal A P.
American Journal of Human Genetics 2022