@misc{10481/79096,
year = {2022},
month = {11},
url = {https://hdl.handle.net/10481/79096},
abstract = {Tinnitus is the phantom percept of an internal non-verbal set of noises and tones. It is reported by 15% of the population and it is
usually associated with hearing and/or brain disorders. The role of structural variants (SVs) in coding and non-coding regions has
not been investigated in patients with severe tinnitus. In this study, we performed whole-genome sequencing in 97 unrelated
Swedish individuals with chronic tinnitus (TIGER cohort). Rare single nucleotide variants (SNV), large structural variants (LSV), and
copy number variations (CNV) were retrieved to perform a gene enrichment analysis in TIGER and in a subgroup of patients with
severe tinnitus (SEVTIN, n = 34), according to the tinnitus handicap inventory (THI) scores. An independent exome sequencing
dataset of 147 Swedish tinnitus patients was used as a replication cohort (JAGUAR cohort) and population-specific datasets from
Sweden (SweGen) and Non-Finish Europeans (NFE) from gnomAD were used as control groups. SEVTIN patients showed a higher
prevalence of hyperacusis, hearing loss, and anxiety when they were compared to individuals in the TIGER cohort. We found an
enrichment of rare missense variants in 6 and 8 high-constraint genes in SEVTIN and TIGER cohorts, respectively. Of note, an
enrichment of missense variants was found in the CACNA1E gene in both SEVTIN and TIGER. We replicated the burden of missense
variants in 9 high-constrained genes in the JAGUAR cohort, including the gene NAV2, when data were compared with NFE.
Moreover, LSVs in constrained regions overlapping CACNA1E, NAV2, and TMEM132D genes were observed in TIGER and SEVTIN.},
organization = {La Caixa Foundation	GNP-182	
100010434	
LCF/PR/DE18/52010002	
H2020-SC1-2019-848261},
organization = {European Commission	848261	
722046},
organization = {Svenska Lakaresalskapet	SLS-779681	
Hoerselforskningsfonden	503	
Tysta Skolan and Forschung Fuer Leben},
organization = {Andalusian Goverment (CECEU)	DOC_01677},
organization = {Sara Borrell postdoctoral Fellowship (ISCIII)	CD20/00153},
organization = {Andalusian Health Government (CSyF 2020 POSTDOC)	RH-0150-2020},
organization = {Swedish Research Council},
organization = {European Commission	2018-05973},
publisher = {Nature},
title = {Using coding and non-coding rare variants to target candidate genes in patients with severe tinnitus},
doi = {10.1038/s41525-022-00341-w},
author = {Gallego Martínez, Álvaro and Escalera Balsera, Alba and Robles Bolívar, Paula and Román Naranjo, Pablo and Frejo, Lidia and Pérez Carpena, Patricia and López Escámez, José Antonio},
}