Genetic variation in RCOR1 is associated with tinnitus in UK Biobank

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. We performed a case-control genome-wide association study for self-reported tinnitus in 172,608 UK Biobank volunteers. 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The research was carried out using the UK Biobank Resource under application number 11516. HRRW was funded by a PhD Studentship Grant, S44, from Action on Hearing Loss. The study was also supported by funding from NIHR UCLH BRC Deafness and Hearing Problems Theme. We would like to thank all the participants of UK Biobank. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: https://www.ukbiobank.ac.uk/ethics/ All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Summary Statistics will be made available on full publication on UK Biobank website and on request