ArticleEBioMedicine2021
Burden of rare variants in synaptic genes in patients with severe tinnitus: An exome based extreme phenotype study.
Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 4 of them syntheses that pooled it.
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Who cites it
29 citing papers in PubMed, 4 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- A Systematic Review on the Role of the Stria Vascularis in Menière's Disease Pathogenesis.Journal of the Association for Research in Otolaryngology : JARO · 2025Pooled it
- A Systematic Review on the Genetic Contribution to Tinnitus.Journal of the Association for Research in Otolaryngology : JARO · 2024Pooled it
- Screening for Circulating Inflammatory Proteins Does Not Reveal Plasma Biomarkers of Constant Tinnitus.Journal of the Association for Research in Otolaryngology : JARO · 2023Pooled it
- Low Evidence for Tinnitus Risk Factors: A Systematic Review and Meta-analysis.Journal of the Association for Research in Otolaryngology : JARO · 2023Pooled it
- Tinnitus and tinnitus disorder: Genetic, neurobiological, and clinical differentiation.iScience · 2026Review
- Tinnitus.Nature reviews. Disease primers · 2026Review
- Article
- Integrating GWAS meta-analysis with human brain cell mapping implicates the amygdala and the midbrain in the pathogenesis of tinnitus.medRxiv : the preprint server for health sciences · 2025Article
- Tinnitus risk factors and its evolution over time.Nature communications · 2025Article
- A Neuron-Like Cellular Model for Severe Tinnitus Associated with Rare Variations in the ANK2 Gene.Molecular neurobiology · 2025Article
- DNA Methylation Patterns Associated with Tinnitus in Young Adults-A Pilot Study.Journal of the Association for Research in Otolaryngology : JARO · 2024Article
- Phenotypic spectrum of tinnitus patients bearing rare ANK2 gene variants.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2024Article
- The genomic landscape of Ménière's disease: a path to endolymphatic hydrops.BMC genomics · 2024Article
- Transcriptional-profile changes in the medial geniculate body after noise-induced tinnitus.Experimental biology and medicine (Maywood, N.J.) · 2024Article
- Article
- Current and Emerging Therapies for Chronic Subjective Tinnitus.Journal of clinical medicine · 2023Review
- Targeting the Limbic System: Insights into Its Involvement in Tinnitus.International journal of molecular sciences · 2023Review
- Transcriptional Profile Changes after Noise-Induced Tinnitus in Rats.Brain sciences · 2023Article
- A genome-wide association study of tinnitus reveals shared genetic links to neuropsychiatric disorders.Scientific reports · 2022Article
- Using coding and non-coding rare variants to target candidate genes in patients with severe tinnitus.NPJ genomic medicine · 2022Article
Corrections and comments
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Authors and funding
12 authors at 10 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundtinnitus is a heterogeneous condition associated with audiological and/or mental disorders. Chronic, severe tinnitus is reported in 1% of the population and it shows a relevant heritability, according to twins, adoptees and familial aggregation studies. The genetic contribution to severe tinnitus is unknown since large genomic studies include individuals with self-reported tinnitus and large heterogeneity in the phenotype. The aim of this study was to identify genes for severe tinnitus in patients with extreme phenotype.
methodsfor this extreme phenotype study, we used three different cohorts with European ancestry (Spanish with Meniere disease (MD), Swedes tinnitus and European generalized epilepsy). In addition, four independent control datasets were also used for comparisons. Whole-exome sequencing was performed for the MD and epilepsy cohorts and whole-genome sequencing was carried out in Swedes with tinnitus.
findingswe found an enrichment of rare missense variants in 24 synaptic genes in a Spanish cohort, the most significant being PRUNE2, AKAP9, SORBS1, ITGAX, ANK2, KIF20B and TSC2 (p < 2E
interpretationa burden of rare variants in ANK2, AKAP9 and TSC2 is associated with severe tinnitus. ANK2, encodes a cytoskeleton scaffolding protein that coordinates the assembly of several proteins, drives axonal branching and influences connectivity in neurons.
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