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Using coding and non-coding rare variants to target candidate genes in patients with severe tinnitus

التفاصيل البيبلوغرافية
العنوان: Using coding and non-coding rare variants to target candidate genes in patients with severe tinnitus
المؤلفون: Alvaro Gallego-Martinez, Alba Escalera-Balsera, Natalia Trpchevska, Paula Robles-Bolivar, Pablo Roman-Naranjo, Lidia Frejo, Patricia Perez-Carpena, Jan Bulla, Silvano Gallus, Barbara Canlon, Christopher R. Cederroth, Jose A. Lopez-Escamez
المصدر: npj Genomic Medicine, Vol 7, Iss 1, Pp 1-9 (2022)
بيانات النشر: Nature Portfolio, 2022.
سنة النشر: 2022
المجموعة: LCC:Medicine
LCC:Genetics
مصطلحات موضوعية: Medicine, Genetics, QH426-470
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2056-7944
Relation: https://doaj.org/toc/2056-7944
DOI: 10.1038/s41525-022-00341-w
URL الوصول: https://doaj.org/article/5734f936892f451682d332dfb3663313
رقم الأكسشن: edsdoj.5734f936892f451682d332dfb3663313
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20567944
DOI:10.1038/s41525-022-00341-w