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

Helena R. R. Wells,Fatin N. Zainul Abidin,Frances M. K. Williams,Sally J. Dawson,Maxim B. Freidin

doi:10.1038/s41598-021-85871-6

Helena R. R. Wells, Fatin N. Zainul Abidin + Show 3 more

Open Access

https://doi.org/10.1038/s41598-021-85871-6

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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.

Highlights

Tinnitus is a prevalent condition in which perception of sound occurs without an external stimulus
For the genome wide association studies (GWAS), samples were further selected based on ethnicity and additional quality control measures which resulted in a final sample size of N = 91,424 for association analysis
We have investigated genetic risk factors for a self-reported tinnitus by performing a GWAS in the UK Biobank (UKBB) with a sample size over 90,000 individuals and identified 3 genome wide significant variant associations at the same locus

Summary

Introduction

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. There is little evidence to support familial segregation of tinnitus except in rare cases but a recent heritability estimate from more than 70,000 twins in the Swedish Twin Registry suggested that tinnitus heritability at 0.4311 This rises to a relatively high rate of 0.68 when the trait is limited to bilateral tinnitus in men only[11], suggesting a higher genetic component in some. How much do these noises worry, annoy or upset you when they are at their worst?

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