ArticleGenome medicine2023
Sex differences in the polygenic architecture of hearing problems in adults.
Article in Genome medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Discovering Age- and Sex-Specific Genetic Risk Factors in Sensorineural Hearing Loss: Genome-Wide Evidence from Large-Scale Biobanks.Journal of the Association for Research in Otolaryngology : JARO · 2026Pooled it
- Genomic and Epigenomic Advances in Hearing Loss: Molecular Mechanisms, Diagnostics, and Emerging Therapies.Journal of personalized medicine · 2026Review
- Polygenic Contribution to Sensorineural Hearing Loss Implicates Novel Risk Loci and Convergence with Congenital Hearing Loss Genes.Journal of the Association for Research in Otolaryngology : JARO · 2026Article
- Multi-ancestry GWAS of age-related hearing loss identifies 140 loci and key cellular mechanisms.Nature communications · 2026Article
- Genome-wide investigation highlights global and local pleiotropy linking neurodevelopmental disorders to acquired hearing problems.Psychological medicine · 2026Article
- Cross-species validation of a human age-related hearing loss candidate KLHDC7B as essential for mammalian hearing.Communications biology · 2025Article
- Large-scale audiometric phenotyping identifies distinct genes and pathways involved in hearing loss subtypes.Communications biology · 2025Article
- Genome-Wide Association Study of Age-Related Hearing Loss in CFW Mice Identifies Multiple Genes and Loci, Including Prkag2.Journal of the Association for Research in Otolaryngology : JARO · 2025Article
- Age-, Sex-, and Ancestry-Specific Prevalence of Hearing Loss in UK Biobank and All of Us Research Program.Aging and disease · 2025Article
- Rheumatoid arthritis and risk of hearing impairment: A genetic correlation and bidirectional Mendelian randomization study.Medicine · 2025Article
- Comparison of associations suggests mainly distinct pools of genetic risk factors contribute to cisplatin-induced hearing loss and hearing difficulty in the general population.Frontiers in pharmacology · 2025Article
- Pharmacological Approaches to Hearing Loss.Pharmacological reviews · 2024Review
- Sex differences in the pleiotropy of hearing difficulty with imaging-derived phenotypes: a brain-wide investigation.Brain : a journal of neurology · 2024Article
- Polygenic Risk Score-Based Association Analysis Identifies Genetic Comorbidities Associated with Age-Related Hearing Difficulty in Two Independent Samples.Journal of the Association for Research in Otolaryngology : JARO · 2024Article
- The cells of the sensory epithelium, and not the stria vascularis, are the main cochlear cells related to the genetic pathogenesis of age-related hearing loss.American journal of human genetics · 2024Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundHearing problems (HP) in adults are common and are associated with several comorbid conditions. Its prevalence increases with age, reflecting the cumulative effect of environmental factors and genetic predisposition. Although several risk loci have been already identified, HP biology and epidemiology are still insufficiently investigated by large-scale genetic studies.
methodsLeveraging the UK Biobank, the Nurses' Health Studies (I and II), the Health Professionals Follow-up Study, and the Million Veteran Program, we conducted a comprehensive genome-wide investigation of HP in 748,668 adult participants (discovery N = 501,825; replication N = 226,043; cross-ancestry replication N = 20,800). We leveraged the GWAS findings to characterize HP polygenic architecture, exploring sex differences, polygenic risk across ancestries, tissue-specific transcriptomic regulation, cause-effect relationships with genetically correlated traits, and gene interactions with HP environmental risk factors.
resultsWe identified 54 risk loci and demonstrated that HP polygenic risk is shared across ancestry groups. Our transcriptomic regulation analysis highlighted the potential role of the central nervous system in HP pathogenesis. The sex-stratified analyses showed several additional associations related to peripheral hormonally regulated tissues reflecting a potential role of estrogen in hearing function. This evidence was supported by the multivariate interaction analysis that showed how genes involved in brain development interact with sex, noise pollution, and tobacco smoking in relation to their HP associations. Additionally, the genetically informed causal inference analysis showed that HP is linked to many physical and mental health outcomes.
conclusionsThe results provide many novel insights into the biology and epidemiology of HP in adults. Our sex-specific analyses and transcriptomic associations highlighted molecular pathways that may be targeted for drug development or repurposing. Additionally, the potential causal relationships identified may support novel preventive screening programs to identify individuals at risk.
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