Genetic predisposition to tinnitus in the UK Biobank population

Abstract Tinnitus, the phantom perception of noise originating from the inner ear, has been reported by 15% of the world’s population, with many patients reporting major deficits to cognition and mood. However, both objective diagnostic tools and targeted therapeutic strategies have yet to be establ...

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Autores principales:	Madeleine E. Urbanek, Jian Zuo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a8670e26bc4e440b8083aac37a29f74a
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spelling	oai:doaj.org-article:a8670e26bc4e440b8083aac37a29f74a2021-12-02T18:50:52ZGenetic predisposition to tinnitus in the UK Biobank population10.1038/s41598-021-97350-z2045-2322https://doaj.org/article/a8670e26bc4e440b8083aac37a29f74a2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97350-zhttps://doaj.org/toc/2045-2322Abstract Tinnitus, the phantom perception of noise originating from the inner ear, has been reported by 15% of the world’s population, with many patients reporting major deficits to cognition and mood. However, both objective diagnostic tools and targeted therapeutic strategies have yet to be established. To better understand the underlying genes that may preclude tinnitus, we performed a genome-wide association study of the UK Biobank’s 49,960 whole exome sequencing participants to identify any loci strongly associated with tinnitus. We identified 17 suggestive single nucleotide polymorphisms (p < 1e−5) spanning 13 genes in two sex-separated cohorts reporting chronic, bothersome tinnitus (control males n = 7,315, tinnitus males n = 226, control females n = 11,732, tinnitus females n = 300). We also found a significant missense mutation in WDPCP (p = 3.959e−10) in the female cohort, a mutation which has been previously implicated in typical neuronal functioning through axonal migration and structural reinforcement, as well as in Bardet-Biedl syndrome-15, a ciliopathy. Additionally, in situ hybridization in the embryonic and P56 mouse brain demonstrated that the majority of these genes are expressed within the dorsal cochlear nucleus, the region of the brain theorized to initially induce tinnitus. Further RT-qPCR and RNAScope data also reveals this expression pattern. The results of this study indicate that predisposition to tinnitus may span across multiple genomic loci and be established by weakened neuronal circuitry and maladaptive cytoskeletal modifications within the dorsal cochlear nucleus.Madeleine E. UrbanekJian ZuoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Madeleine E. Urbanek Jian Zuo Genetic predisposition to tinnitus in the UK Biobank population
description	Abstract Tinnitus, the phantom perception of noise originating from the inner ear, has been reported by 15% of the world’s population, with many patients reporting major deficits to cognition and mood. However, both objective diagnostic tools and targeted therapeutic strategies have yet to be established. To better understand the underlying genes that may preclude tinnitus, we performed a genome-wide association study of the UK Biobank’s 49,960 whole exome sequencing participants to identify any loci strongly associated with tinnitus. We identified 17 suggestive single nucleotide polymorphisms (p < 1e−5) spanning 13 genes in two sex-separated cohorts reporting chronic, bothersome tinnitus (control males n = 7,315, tinnitus males n = 226, control females n = 11,732, tinnitus females n = 300). We also found a significant missense mutation in WDPCP (p = 3.959e−10) in the female cohort, a mutation which has been previously implicated in typical neuronal functioning through axonal migration and structural reinforcement, as well as in Bardet-Biedl syndrome-15, a ciliopathy. Additionally, in situ hybridization in the embryonic and P56 mouse brain demonstrated that the majority of these genes are expressed within the dorsal cochlear nucleus, the region of the brain theorized to initially induce tinnitus. Further RT-qPCR and RNAScope data also reveals this expression pattern. The results of this study indicate that predisposition to tinnitus may span across multiple genomic loci and be established by weakened neuronal circuitry and maladaptive cytoskeletal modifications within the dorsal cochlear nucleus.
format	article
author	Madeleine E. Urbanek Jian Zuo
author_facet	Madeleine E. Urbanek Jian Zuo
author_sort	Madeleine E. Urbanek
title	Genetic predisposition to tinnitus in the UK Biobank population
title_short	Genetic predisposition to tinnitus in the UK Biobank population
title_full	Genetic predisposition to tinnitus in the UK Biobank population
title_fullStr	Genetic predisposition to tinnitus in the UK Biobank population
title_full_unstemmed	Genetic predisposition to tinnitus in the UK Biobank population
title_sort	genetic predisposition to tinnitus in the uk biobank population
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a8670e26bc4e440b8083aac37a29f74a
work_keys_str_mv	AT madeleineeurbanek geneticpredispositiontotinnitusintheukbiobankpopulation AT jianzuo geneticpredispositiontotinnitusintheukbiobankpopulation
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Genetic predisposition to tinnitus in the UK Biobank population

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