biostudies-literatureClifford REBLRD VARRD VAU.S. Department of Veterans AffairsCSRD VA614https://www.ebi.ac.uk/biostudies/studies/S-EPMC10799010biostudies-literatureUnknown15(1)Tinnitus is a heritable, highly prevalent auditory disorder treated by multiple medical specialties. Previous GWAS indicated high genetic correlations between tinnitus and hearing loss, with little indication of differentiating signals. We present a GWAS meta-analysis, triple previous sample sizes, and expand to non-European ancestries. GWAS in 596,905 Million Veteran Program subjects identified 39 tinnitus loci, and identified genes related to neuronal synapses and cochlear structural support. Applying state-of-the-art analytic tools, we confirm a large number of shared variants, but also a distinct genetic architecture of tinnitus, with higher polygenicity and large proportion of variants not shared with hearing difficulty. Tissue-expression analysis for tinnitus infers broad enrichment Nature communicationsGenetic architecture distinguishes tinnitus from hearing loss.PMC10799010I01 BX005920RX004293I01 RX004293IK2 CX002107I01 RX002744I01 BX001205BX005920Stein MBColeman JRIDaskalakis NPZuo YTelese FClifford REMaihofer AXGasperi MNievergelt CMChatzinakos CMikita EARyan AFTcheandjieu CHogan KfalseGenetic architecture distinguishes tinnitus from hearing loss.Tinnitus is a heritable, highly prevalent auditory disorder treated by multiple medical specialties. Previous GWAS indicated high genetic correlations between tinnitus and hearing loss, with little indication of differentiating signals. We present a GWAS meta-analysis, triple previous sample sizes, and expand to non-European ancestries. GWAS in 596,905 Million Veteran Program subjects identified 39 tinnitus loci, and identified genes related to neuronal synapses and cochlear structural support. Applying state-of-the-art analytic tools, we confirm a large number of shared variants, but also a distinct genetic architecture of tinnitus, with higher polygenicity and large proportion of variants not shared with hearing difficulty. Tissue-expression analysis for tinnitus infers broad enrichment 2024-01-01T00:00:00Z2024 Jan2026-06-02T06:52:14.128Z2025-04-04T19:22:13.942ZS-EPMC107990103824289910.1038/s41467-024-44842-x