TY - JOUR
T1 - Genetic architecture distinguishes tinnitus from hearing loss
AU - Clifford, Royce E.
AU - Maihofer, Adam X.
AU - Chatzinakos, Chris
AU - Coleman, Jonathan R.I.
AU - Daskalakis, Nikolaos P.
AU - Gasperi, Marianna
AU - Hogan, Kelleigh
AU - Mikita, Elizabeth A.
AU - Stein, Murray B.
AU - Tcheandjieu, Catherine
AU - Telese, Francesca
AU - Zuo, Yanning
AU - Ryan, Allen F.
AU - Nievergelt, Caroline M.
N1 - Publisher Copyright:
© 2024, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
PY - 2024/12
Y1 - 2024/12
N2 - 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 across most brain tissues, in contrast to hearing difficulty. Finally, tinnitus is not only correlated with hearing loss, but also with a spectrum of psychiatric disorders, providing potential new avenues for treatment. This study establishes tinnitus as a distinct disorder separate from hearing difficulties.
AB - 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 across most brain tissues, in contrast to hearing difficulty. Finally, tinnitus is not only correlated with hearing loss, but also with a spectrum of psychiatric disorders, providing potential new avenues for treatment. This study establishes tinnitus as a distinct disorder separate from hearing difficulties.
UR - http://www.scopus.com/inward/record.url?scp=85182699696&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-44842-x
DO - 10.1038/s41467-024-44842-x
M3 - Article
C2 - 38242899
AN - SCOPUS:85182699696
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 614
ER -