Tinnitus Treatment Report

www.TinnitusTreatmentReport.com

gene therapy

University of Granada researchers identify genes linked to severe tinnitus

https://www.audiology-worldnews.com/research/4082-university-of-granada-researchers-identify-genes-linked-to-tinnitus

Studying tinnitus linked to different disorders can lead to the identification of molecular mechanisms, early diagnosis, and the application of new drugs for treating tinnitus.

https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(21)00102-X/fulltext

University of Granada researchers identify genes linked to tinnitus

Added value of this study

We have found a significant enrichment of missense rare variants in synaptic genes including ANK2, TSC2 and AKAP9 in patients with tinnitus extreme phenotype in Meniere disease patients. We also replicated these findings in an independent cohort of tinnitus patients from Sweden. Gene ontology (GO) and gene-set enrichment analyses revealed several pathways and biological processes involved in severe tinnitus, the top GO terms being membrane trafficking and cytoskeletal protein binding in neurons.

This is the first study reporting the association of rare variation in ANK2, TSC2 and, AKAP9 genes with severe tinnitus and supports the involvement of membrane trafficking and cytoskeletal protein binding in the pathophysiology of severe tinnitus.

The bewitched ear: State of the art genomics research on tinnitus

CATEGORY:
Research

TITLE:
The bewitched ear: State of the art genomics research on tinnitus

DESCRIPTION:
No abstract

CONTENT:
EBioMedicine. 2021 Apr 24;67:103349. doi: 10.1016/j.ebiom.2021.103349. Online ahead of print.

NO ABSTRACT

PMID:33906065 | DOI:10.1016/j.ebiom.2021.103349

SOURCE:
EBioMedicine

DATE – PUBLISHED:
2021-04-25T03:17:37Z

DATE – DOI: 2021-04-25T03:17:37Z
DATE – PUBMED: 2021 Apr 24
DATE OUTPUT MATCHED: True

DATE – ADDED:
Tue, 27 Apr 2021 06:00:00 -0400

DATE – RETRIEVED:
04/28/21 06:25AM
2021-04-28T06:25:10-04:00

IDENTIFIER:
pmid:33906065,doi:10.1016/j.ebiom.2021.103349

PUBMED ID:
pubmed:33906065

DOI:
10.1016/j.ebiom.2021.103349

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33906065/

LINK – DOI:
https://doi.org/10.1016/j.ebiom.2021.103349

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S2352396421001420

https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(21)00142-0/fulltext

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-04-28T06:25:10-04:00, www.tinnitustreatmentreport.com.

Burden of rare variants in synaptic genes in patients with severe tinnitus: An exome based extreme phenotype study

CATEGORY:
Research

TITLE:
Burden of rare variants in synaptic genes in patients with severe tinnitus: An exome based extreme phenotype study

DESCRIPTION:
BACKGROUND: tinnitus is a heterogeneous condition associated with audiological and/or mental disorders. Chronic, severe tinnitus is reported in 1% of the population and it shows a relevant heritability, according to twins, adoptees and familial aggregation studies. The genetic contribution to severe tinnitus is unknown since large genomic studies include individuals with self-reported tinnitus and large heterogeneity in the phenotype. The aim of this study was to identify genes for severe…

CONTENT:
EBioMedicine. 2021 Apr 1;66:103309. doi: 10.1016/j.ebiom.2021.103309. Online ahead of print.

ABSTRACT

BACKGROUND: tinnitus is a heterogeneous condition associated with audiological and/or mental disorders. Chronic, severe tinnitus is reported in 1% of the population and it shows a relevant heritability, according to twins, adoptees and familial aggregation studies. The genetic contribution to severe tinnitus is unknown since large genomic studies include individuals with self-reported tinnitus and large heterogeneity in the phenotype. The aim of this study was to identify genes for severe tinnitus in patients with extreme phenotype.

METHODS: for this extreme phenotype study, we used three different cohorts with European ancestry (Spanish with Meniere disease (MD), Swedes tinnitus and European generalized epilepsy). In addition, four independent control datasets were also used for comparisons. Whole-exome sequencing was performed for the MD and epilepsy cohorts and whole-genome sequencing was carried out in Swedes with tinnitus.

FINDINGS: we found an enrichment of rare missense variants in 24 synaptic genes in a Spanish cohort, the most significant being PRUNE2, AKAP9, SORBS1, ITGAX, ANK2, KIF20B and TSC2 (p < 2E-04 ), when they were compared with reference datasets. This burden was replicated for ANK2 gene in a Swedish cohort with 97 tinnitus individuals, and in a subset of 34 Swedish patients with severe tinnitus for ANK2, AKAP9 and TSC2 genes (p < 2E-02 ). However, these associations were not significant in a third cohort of 701 generalized epilepsy individuals without tinnitus. Gene ontology (GO) and gene-set enrichment analyses revealed several pathways and biological processes involved in severe tinnitus, including membrane trafficking and cytoskeletal protein binding in neurons. INTERPRETATION: a burden of rare variants in ANK2, AKAP9 and TSC2 is associated with severe tinnitus. ANK2, encodes a cytoskeleton scaffolding protein that coordinates the assembly of several proteins, drives axonal branching and influences connectivity in neurons. PMID:33813136 | DOI:10.1016/j.ebiom.2021.103309 SOURCE: EBioMedicine DATE - PUBLISHED: 2021-04-02T07:03:04Z DATE - DOI: 2021-04-02T07:03:04Z DATE - PUBMED: 2021 Apr 1 DATE OUTPUT MATCHED: True DATE - ADDED: Sun, 04 Apr 2021 06:00:00 -0400 DATE - RETRIEVED: 04/05/21 01:42AM 2021-04-05T01:42:04-04:00 IDENTIFIER: pmid:33813136,doi:10.1016/j.ebiom.2021.103309 PUBMED ID: pubmed:33813136 DOI: 10.1016/j.ebiom.2021.103309 LINK - PUBMED: https://pubmed.ncbi.nlm.nih.gov/33813136/ LINK - DOI: https://doi.org/10.1016/j.ebiom.2021.103309 LINK - PUBLISHER: https://linkinghub.elsevier.com/retrieve/pii/S235239642100102X REFERENCES: Tinnitus Treatment Report, Urgent Research, 2021-04-05T01:42:04-04:00, www.tinnitustreatmentreport.com.

Genome-wide association study suggests that variation at the RCOR1 locus is associated with tinnitus in UK Biobank

CATEGORY:
Research

TITLE:
Genome-wide association study suggests that variation at the RCOR1 locus is associated with tinnitus in UK Biobank

DESCRIPTION:
Tinnitus is a prevalent condition in which perception of sound occurs without an external stimulus. It is often associated with pre-existing hearing loss or noise-induced damage to the auditory system. In some individuals it occurs frequently or even continuously and leads to considerable distress and difficulty sleeping. There is little knowledge of the molecular mechanisms involved in tinnitus which has hindered the development of treatments. Evidence suggests that tinnitus has a heritable…

CONTENT:
Sci Rep. 2021 Mar 19;11(1):6470. doi: 10.1038/s41598-021-85871-6.

ABSTRACT

Tinnitus is a prevalent condition in which perception of sound occurs without an external stimulus. It is often associated with pre-existing hearing loss or noise-induced damage to the auditory system. In some individuals it occurs frequently or even continuously and leads to considerable distress and difficulty sleeping. There is little knowledge of the molecular mechanisms involved in tinnitus which has hindered the development of treatments. Evidence suggests that tinnitus has a heritable component although previous genetic studies have not established specific risk factors. From a total of 172,608 UK Biobank participants who answered questions on tinnitus we performed a case-control genome-wide association study for self-reported tinnitus. Final sample size used in association analysis was N = 91,424. Three variants in close proximity to the RCOR1 gene reached genome wide significance: rs4906228 (p = 1.7E-08), rs4900545 (p = 1.8E-08) and 14:103042287_CT_C (p = 3.50E-08). RCOR1 encodes REST Corepressor 1, a component of a co-repressor complex involved in repressing neuronal gene expression in non-neuronal cells. Eleven other independent genetic loci reached a suggestive significance threshold of p < 1E-06. PMID:33742053 | DOI:10.1038/s41598-021-85871-6 SOURCE: Scientific reports DATE - PUBLISHED: 2021-03-19T13:06:54Z DATE - DOI: 2021-03-19T13:06:54Z DATE - PUBMED: 2021 Mar 19 DATE OUTPUT MATCHED: True DATE - ADDED: Sat, 20 Mar 2021 06:00:00 -0400 DATE - RETRIEVED: 03/20/21 05:25PM 2021-03-20T17:25:35-04:00 IDENTIFIER: pmid:33742053,doi:10.1038/s41598-021-85871-6 PUBMED ID: pubmed:33742053 DOI: 10.1038/s41598-021-85871-6 LINK - PUBMED: https://pubmed.ncbi.nlm.nih.gov/33742053/ LINK - DOI: https://doi.org/10.1038/s41598-021-85871-6 LINK - PUBLISHER: http://www.nature.com/articles/s41598-021-85871-6 REFERENCES: Tinnitus Treatment Report, Urgent Research, 2021-03-20T17:25:35-04:00, www.tinnitustreatmentreport.com.

A New Buzz for Tinnitus—It’s in the Genes!

https://jamanetwork.com/journals/jamaotolaryngology/article-abstract/2770968

September 24, 2020
A New Buzz for Tinnitus—It’s in the Genes!
Christopher R. Cederroth, PhD1,2,3; Natalia Trpchevska, MD3; Berthold Langguth, MD, PhD4
Author Affiliations
JAMA Otolaryngol Head Neck Surg. Published online September 24, 2020. doi:10.1001/jamaoto.2020.2919

Possible tinnitus gene found: Genetic variation in RCOR1 is associated with tinnitus

The new study identifies candidate genes that could reveal the underlying causes and molecular mechanisms involved in tinnitus and ultimately lead to new targeted treatments.

“Our study has identified a number of interesting candidate genes for further investigation, most notably RCOR1,” write the study authors.

The preprint, which was posted to medRxiv on September 13, 2020, has not yet been certified by peer review but it was supported by funding from some big names such as Action on Hearing Loss and NIHR UCLH BRC (Deafness and Hearing Problems).

March 21, 2021 update: This research has now been peer-reviewed and was recently published in Scientific Reports (Nature). https://www.nature.com/articles/s41598-021-85871-6

Researchers performed a genome-wide association study of tinnitus involving 172,608 volunteers.

Identification of the genetic variants involved in tinnitus would help reveal the nature of the mechanisms involved in generating tinnitus after hearing loss, a requisite for development of treatments. Previous pilot genome-wide association studies and candidate gene studies for tinnitus have lacked sufficient power to establish specific genetic risk factors but the relatively high heritability demonstrates there is potential to use such approaches to reveal the underlying mechanisms.

“Three variants in close proximity to the RCOR1 gene reached genome wide significance,” according to the study.

Worth a read.

Link to peer-reviewed paper (full text):

https://www.nature.com/articles/s41598-021-85871-6

Link to preprint abstract:

https://doi.org/10.1101/2020.09.11.20192583

Link to preprint [PDF]:

https://www.medrxiv.org/content/10.1101/2020.09.11.20192583v1.full.pdf

The authors responsible for this fascinating paper (preprint) now at the forefront of the genetics of tinnitus: Helena Rose Rees Wells, Fatin N Zainul Abidin, Maxim Freydin, Frances MK Williams, Sally J Dawson.

It is therefore possible that the association of MYO3B, ARID5B and ZNF318 with tinnitus is secondary to their role in hearing since tinnitus is usually manifested when there is a hearing loss present. However, it may be that the nature of the hearing loss caused by these genes variants creates a deficit which particularly potentiates the generation of tinnitus.

More “tinnitus gene” coverage to follow…

How to follow this research (and get news about upcoming treatments such as FX-322, GW-201, and the Susan Shore device)? Keep checking the front page – OR – subscribe to the free email newsletter for treatment updates, including a once-weekly summary of new links that were added to this site.

References

Wells, H.R.R., Abidin, F.N.Z., Freidin, M.B. et al. Genome-wide association study suggests that variation at the RCOR1 locus is associated with tinnitus in UK Biobank. Sci Rep 11, 6470 (2021). https://doi.org/10.1038/s41598-021-85871-6

Comments? Corrections? Questions? Email michael@urgentresearch.com (admin) and say hello.

Genetic variation in RCOR1 is associated with tinnitus in UK Biobank [Preprint]

https://www.medrxiv.org/content/medrxiv/early/2020/09/13/2020.09.11.20192583.full.pdf

Genetic variation in RCOR1 is associated with tinnitus in UK Biobank

Helena Rose Rees Wells, Fatin N Zainul Abidin, Maxim Freydin, Frances MK Williams, Sally J Dawson

doi: https://doi.org/10.1101/2020.09.11.20192583

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

Single nucleotide polymorphisms in tinnitus patients exhibiting severe distress: severity of tinnitus is associated with genetic background

https://www.nature.com/articles/s41598-020-69467-0

https://doi.org/10.1038/s41598-020-69467-0

https://pubmed.ncbi.nlm.nih.gov/32747715/

TITLE:
Single nucleotide polymorphisms in tinnitus patients exhibiting severe distress

ALTERNATIVE TITLE:
None

DATE:
Tue, 04 Aug 2020 06:00:00 -0400

AUTHORS:
Takahisa Watabe,Sho Kanzaki,Noriko Sato,Tatsuo Matsunaga,Masaaki Muramatsu,Kaoru Ogawa

SOURCE:
Scientific reports

DESCRIPTION:

The association between distress caused by tinnitus and psychological factors such as depression and anxiety has been examined and reported. However, prognostic factors remain poorly understood because there are only a few reports on genetic associations. We theorized there might be an association between the grade of tinnitus distress and the genetic background related to psychological factors which might lead us to identify prognostic markers. We enrolled 138 patients who had suffered from…

CONTENT:

Sci Rep. 2020 Aug 3;10(1):13023. doi: 10.1038/s41598-020-69467-0.

ABSTRACT

The association between distress caused by tinnitus and psychological factors such as depression and anxiety has been examined and reported. However, prognostic factors remain poorly understood because there are only a few reports on genetic associations. We theorized there might be an association between the grade of tinnitus distress and the genetic background related to psychological factors which might lead us to identify prognostic markers. We enrolled 138 patients who had suffered from tinnitus for over 3 months. Using Tinnitus Handicap Inventory (THI) scores, we examined the association between tinnitus distress and a genetic background related to depression or anxiety. A significant association between single nucleotide polymorphism rs131702 of the Breakpoint Cluster Region (BCR) gene and the severe THI score was identified. In addition, there was an association with the severity of the State-Trait Anxiety Inventory, an index of state anxiety severity. No association was found with the Self-Rating Depression Scale, an index of depression severity. It is reported that rs131702 of BCR in Japanese patients are related to bipolar II depression characterized by fluctuation between abnormal mood states of mania and depression. Our results indicate that rs131702 of BCR is independent of depression in this study and is, therefore, a prognostic factor unique to tinnitus. We conclude that the severity of tinnitus is associated with genes related to depression.

PMID:32747715 | DOI:10.1038/s41598-020-69467-0

PUBMED ID:
pubmed:32747715

OTHER ID:
pmid:32747715,doi:10.1038/s41598-020-69467-0

PUBLICATION DATE:
Tue, 04 Aug 2020 06:00:00 -0400
2020-08-05

RETRIEVAL DATE :
08/04/20 06:46AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/32747715/?utm_source=MS-Office&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1raUxiGThRUW-m52df5Bb_DZzfOiKEExmPo2D4RXGu6sfr6ozK&fc=20200430165258&ff=20200804064627&v=2.11.4

LINK – DOI:
https://doi.org/10.1038/s41598-020-69467-0

LINK – FULL TEXT:
Pending

NOTES:
None

Genetic Inheritance and Its Contribution to Tinnitus

https://link.springer.com/chapter/10.1007%2F7854_2020_155

https://doi.org/10.1007/7854_2020_155

https://pubmed.ncbi.nlm.nih.gov/32705497/

TITLE:
Genetic Inheritance and Its Contribution to Tinnitus

ALTERNATIVE TITLE:
None

DATE:
Fri, 24 Jul 2020 06:00:00 -0400

AUTHORS:
Sana Amanat,Alvaro Gallego-Martinez,Jose A Lopez-Escamez

SOURCE:
Current topics in behavioral neurosciences

DESCRIPTION:

Tinnitus is the abnormal perception of sound that affects more than 15% of adult population around the globe. Severe tinnitus is considered a complex disorder that arises as result of the interaction of genetic and environmental factors, and it is associated with several comorbidities such as hearing loss, anxiety, and insomnia. We begin this review with an introduction to human molecular genetics and the role of genetic variation on the inheritance. There are some genetic reports on tinnitus…

CONTENT:

Curr Top Behav Neurosci. 2020 Jul 24. doi: 10.1007/7854_2020_155. Online ahead of print.

ABSTRACT

Tinnitus is the abnormal perception of sound that affects more than 15% of adult population around the globe. Severe tinnitus is considered a complex disorder that arises as result of the interaction of genetic and environmental factors, and it is associated with several comorbidities such as hearing loss, anxiety, and insomnia. We begin this review with an introduction to human molecular genetics and the role of genetic variation on the inheritance. There are some genetic reports on tinnitus heritability including concordance studies in twins and adoptees or aggregation in families providing some evidence for familial aggregation in patients with severe tinnitus and high concordance in monozygotic twins with bilateral tinnitus. So, sex differences in familial aggregation and heritability of bilateral tinnitus suggest a potential sexual dimorphism in tinnitus inheritance.Molecular genetic studies have been demonstrated to be a useful tool to understand the role of genetic variation in rare diseases and complex disorders. The reported associations in common variants in neurotrophic factors such as GDNF, BDNF, or potassium channels genes were underpowered, and the lack of replication questions these findings. Although candidate gene approaches have failed in replicating these genetic associations, the development of high throughput sequencing technology and the selection of extreme phenotypes are strategies that will allow the clinicians and researchers to combine genetic information with clinical data to implement a personalized diagnosis and therapy in patients with tinnitus.

PMID:32705497 | DOI:10.1007/7854_2020_155

PUBMED ID:
pubmed:32705497

OTHER ID:
pmid:32705497,doi:10.1007/7854_2020_155

PUBLICATION DATE:
Fri, 24 Jul 2020 06:00:00 -0400
2020-07-25

RETRIEVAL DATE :
07/24/20 11:47AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/32705497/?utm_source=MS-Office&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1raUxiGThRUW-m52df5Bb_DZzfOiKEExmPo2D4RXGu6sfr6ozK&fc=20200430165258&ff=20200724114722&v=2.11.2

LINK – DOI:
https://doi.org/10.1007/7854_2020_155

LINK – FULL TEXT:
Pending

NOTES:
None

Heritability and Genetics Contribution to Tinnitus

https://www.ncbi.nlm.nih.gov/pubmed/32334875?dopt=Abstract

https://www.sciencedirect.com/science/article/abs/pii/S0030666520300396?via%3Dihub

Heritability and Genetics Contribution to Tinnitus

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