Accurate phenotypic classification and exome sequencing allow identification of novel genes and variants associated with adult-onset hearing loss.

Autor: Lewis MA; Wolfson Centre for Age-Related Diseases, King's College London, United Kingdom.; The Medical University of South Carolina, Charleston, South Carolina, United States of America., Schulte J; The Medical University of South Carolina, Charleston, South Carolina, United States of America., Matthews L; The Medical University of South Carolina, Charleston, South Carolina, United States of America., Vaden KI Jr; The Medical University of South Carolina, Charleston, South Carolina, United States of America., Steves CJ; Department of Twin Research and Genetic Epidemiology, King's College London, School of Life Course and Population Sciences, London, United Kingdom., Williams FMK; Department of Twin Research and Genetic Epidemiology, King's College London, School of Life Course and Population Sciences, London, United Kingdom., Schulte BA; The Medical University of South Carolina, Charleston, South Carolina, United States of America., Dubno JR; The Medical University of South Carolina, Charleston, South Carolina, United States of America., Steel KP; Wolfson Centre for Age-Related Diseases, King's College London, United Kingdom.; The Medical University of South Carolina, Charleston, South Carolina, United States of America.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2023 Nov 27; Vol. 19 (11), pp. e1011058. Date of Electronic Publication: 2023 Nov 27 (Print Publication: 2023).
DOI: 10.1371/journal.pgen.1011058
Abstrakt: Adult-onset progressive hearing loss is a common, complex disease with a strong genetic component. Although to date over 150 genes have been identified as contributing to human hearing loss, many more remain to be discovered, as does most of the underlying genetic diversity. Many different variants have been found to underlie adult-onset hearing loss, but they tend to be rare variants with a high impact upon the gene product. It is likely that combinations of more common, lower impact variants also play a role in the prevalence of the disease. Here we present our exome study of hearing loss in a cohort of 532 older adult volunteers with extensive phenotypic data, including 99 older adults with normal hearing, an important control set. Firstly, we carried out an outlier analysis to identify genes with a high variant load in older adults with hearing loss compared to those with normal hearing. Secondly, we used audiometric threshold data to identify individual variants which appear to contribute to different threshold values. We followed up these analyses in a second cohort. Using these approaches, we identified genes and variants linked to better hearing as well as those linked to worse hearing. These analyses identified some known deafness genes, demonstrating proof of principle of our approach. However, most of the candidate genes are novel associations with hearing loss. While the results support the suggestion that genes responsible for severe deafness may also be involved in milder hearing loss, they also suggest that there are many more genes involved in hearing which remain to be identified. Our candidate gene lists may provide useful starting points for improved diagnosis and drug development.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Lewis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje