RCOR1

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

March 19, 2021

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.

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

September 14, 2020

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]

September 13, 2020

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.