Large-scale genome-wide association studies (GWAS) show that tinnitus has a modest degree of heritability and sheds more light on its association with neuropsychiatric disorders. "By analyzing DNA from hundreds of thousands of individuals around the world, we have uncovered specific genetic anomalies associated with 'ringing in the ears,'" Dr. Royce E. Clifford of the University of California, San Diego, told Reuters Health by email. "These findings represent a first step towards tailoring a specific intervention for a disorder that until now has eluded definitive cure." Despite its prevalence, there is no objective biomarker for the diagnosis of tinnitus, Dr. Clifford and colleagues note in JAMA Otolaryngology-Head and Neck Surgery. Previous small candidate-gene studies have failed to establish replicable associations with tinnitus, they add. The researchers conducted a GWAS of self-reported tinnitus and hearing using data from almost 173,000 participants in the UK Biobank (UKB). Data from more than 260,000 participants in the US Million Veteran Program (MVP) was used to confirm replication. Analyses of single nucleotide variation in more than 155,000 unrelated participants in the UKB showed that these accounted for about 6% of tinnitus heritability. The researchers also identified six independent loci and 27 genes associated with tinnitus. Of these, three loci and eight genes were replicated in the MVP cohort. The researchers also found genetic correlations with hearing loss, neuroticism, major depressive disorder, insomnia, years of schooling, and measures of well-being. However, these findings were based on participants with European ancestry and, they add, wider studies are required for fine mapping and refining of effect loci. The authors note that "given the substantial genetic and clinical overlap between tinnitus and hearing loss, examining their shared and nonshared genetic aspects will be critical for possible prevention and cure of this pervasive disorder." Dr. Christopher R. Cederroth of the University of Nottingham, UK, who co-wrote an accompanying editorial, told Reuters Health by email, "To me, this is the first time that genetic biomarkers are identified and replicated in an independent cohort. This indicates that tinnitus has the possibility to be defined by other means than self-report, which means that it cannot be considered solely as a symptom of another condition." "Of course," he added, "there are a large number of people with tinnitus who may not have the biomarkers and a large number of people with the marker who may not have tinnitus, and more work is required to understand the genetic basis of tinnitus. This study is a first step towards new definitions of tinnitus as a neurological disorder." —David Douglas Source
