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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: Gallego-Martinez, Alvaro, Escalera-Balsera, Alba, Trpchevska, Natalia, Robles-Bolivar, Paula, Roman-Naranjo, Pablo, Frejo, Lidia, Perez-Carpena, Patricia, Bulla, Jan, Gallus, Silvano, Canlon, Barbara, Cederroth, Christopher R. R., Lopez-Escamez, Jose A. A.
المساهمون: Gallego-Martinez, Alvaro Univ Granada, Ctr Genom & Oncol Res Pfizer, Dept Genom Med, Otol & Neurotol Grp CTS495,GENYO,Andalusian Reg Go, Ave Ilustrac 114, Granada 18016, Spain, Escalera-Balsera, Alba Univ Granada, Ctr Genom & Oncol Res Pfizer, Dept Genom Med, Otol & Neurotol Grp CTS495,GENYO,Andalusian Reg Go, Ave Ilustrac 114, Granada 18016, Spain, Robles-Bolivar, Paula Univ Granada, Ctr Genom & Oncol Res Pfizer, Dept Genom Med, Otol & Neurotol Grp CTS495,GENYO,Andalusian Reg Go, Ave Ilustrac 114, Granada 18016, Spain, Roman-Naranjo, Pablo Univ Granada, Ctr Genom & Oncol Res Pfizer, Dept Genom Med, Otol & Neurotol Grp CTS495,GENYO,Andalusian Reg Go, Ave Ilustrac 114, Granada 18016, Spain, Frejo, Lidia Univ Granada, Ctr Genom & Oncol Res Pfizer, Dept Genom Med, Otol & Neurotol Grp CTS495,GENYO,Andalusian Reg Go, Ave Ilustrac 114, Granada 18016, Spain, Perez-Carpena, Patricia Univ Granada, Ctr Genom & Oncol Res Pfizer, Dept Genom Med, Otol & Neurotol Grp CTS495,GENYO,Andalusian Reg Go, Ave Ilustrac 114, Granada 18016, Spain, Lopez-Escamez, Jose A. A. Univ Granada, Ctr Genom & Oncol Res Pfizer, Dept Genom Med, Otol & Neurotol Grp CTS495,GENYO,Andalusian Reg Go, Ave Ilustrac 114, Granada 18016, Spain, Gallego-Martinez, Alvaro Hosp Univ Virgen de las Nieves, Inst Invest Biosanit, Ibs Granada, Dept Otolaryngol, Granada 18014, Spain, Escalera-Balsera, Alba Hosp Univ Virgen de las Nieves, Inst Invest Biosanit, Ibs Granada, Dept Otolaryngol, Granada 18014, Spain, Robles-Bolivar, Paula Hosp Univ Virgen de las Nieves, Inst Invest Biosanit, Ibs Granada, Dept Otolaryngol, Granada 18014, Spain, Roman-Naranjo, Pablo Hosp Univ Virgen de las Nieves, Inst Invest Biosanit, Ibs Granada, Dept Otolaryngol, Granada 18014, Spain, Frejo, Lidia Hosp Univ Virgen de las Nieves, Inst Invest Biosanit, Ibs Granada, Dept Otolaryngol, Granada 18014, Spain, Perez-Carpena, Patricia Hosp Univ Virgen de las Nieves, Inst Invest Biosanit, Ibs Granada, Dept Otolaryngol, Granada 18014, Spain, Lopez-Escamez, Jose A. A. Hosp Univ Virgen de las Nieves, Inst Invest Biosanit, Ibs Granada, Dept Otolaryngol, Granada 18014, Spain, Gallego-Martinez, Alvaro CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Sensorineural Pathol Programme, Madrid 28029, Spain, Escalera-Balsera, Alba CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Sensorineural Pathol Programme, Madrid 28029, Spain, Robles-Bolivar, Paula CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Sensorineural Pathol Programme, Madrid 28029, Spain, Roman-Naranjo, Pablo CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Sensorineural Pathol Programme, Madrid 28029, Spain, Frejo, Lidia CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Sensorineural Pathol Programme, Madrid 28029, Spain, Perez-Carpena, Patricia CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Sensorineural Pathol Programme, Madrid 28029, Spain, Lopez-Escamez, Jose A. A. CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Sensorineural Pathol Programme, Madrid 28029, Spain, Trpchevska, Natalia Karolinska Inst, Dept Physiol & Pharmacol, Sect Expt Audiol, S-17177 Stockholm, Sweden, Canlon, Barbara Karolinska Inst, Dept Physiol & Pharmacol, Sect Expt Audiol, S-17177 Stockholm, Sweden, Cederroth, Christopher R. R. Karolinska Inst, Dept Physiol & Pharmacol, Sect Expt Audiol, S-17177 Stockholm, Sweden, Perez-Carpena, Patricia Univ Granada, Dept Surg, Div Otolaryngol, Granada 18016, Spain, Lopez-Escamez, Jose A. A. Univ Granada, Dept Surg, Div Otolaryngol, Granada 18016, Spain, Bulla, Jan Univ Bergen, Dept Math, N-5020 Bergen, Norway, Bulla, Jan Univ Regensburg, Dept Psychiat & Psychotherapy, D-93053 Regensburg, Germany, Gallus, Silvano Ist Ric Farmacol Mario Negri IRCCS, Dept Environm Hlth Sci, I-20156 Milan, Italy, Cederroth, Christopher R. R. Nottingham Univ Hosp NHS Trust, Natl Inst Hlth Res NIHR, Nottingham Biomed Res Ctr, Ropewalk House, Nottingham NG1 5DU, England, Cederroth, Christopher R. R. Univ Nottingham, Sch Med, Div Clin Neurosci, Hearing Sci, Nottingham NG7 2UH, England, "La Caixa" Foundation, European Union, Svenska Lakaresalskapet, Hoerselforskningsfonden, Tysta Skolan and Forschung Fuer Leben, Andalusian Goverment (CECEU), Sara Borrell postdoctoral Fellowship (ISCIII), Andalusian Health Government (CSyF 2020 POSTDOC), Swedish Research Council
بيانات النشر: Nature portfolio
سنة النشر: 2022
المجموعة: Sistema Sanitario Público de Andalucía (SSPA): Repositorio
مصطلحات موضوعية: Joint consensus recommendation, Structural variants, Mammalian homolog, Medical genetics, American-college, Association, Mechanisms, Guidelines, Standards, Framework
الوصف: 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 in journal/newspaper
اللغة: English
تدمد: 2056-7944
العلاقة: http://hdl.handle.net/10668/19555Test; https://www.nature.com/articles/s41525-022-00341-w.pdfTest; 892976200001
DOI: 10.1038/s41525-022-00341-w
الإتاحة: https://doi.org/10.1038/s41525-022-00341-wTest
http://hdl.handle.net/10668/19555Test
https://www.nature.com/articles/s41525-022-00341-w.pdfTest
حقوق: Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0Test/ ; open access
رقم الانضمام: edsbas.BAB15399
قاعدة البيانات: BASE
الوصف
تدمد:20567944
DOI:10.1038/s41525-022-00341-w