“Does tinnitus run in your family?” Seldom is that question asked by clinicians to their patients with tinnitus, but why would they ask? Audiologists and ear, nose, and throat specialists see patients with tinnitus in association with either conductive or sensorineural hearing loss, which has led to the clinical dogma that tinnitus is secondary and by definition a symptom arising from the hearing disorder. However, tinnitus may occur in absence of any detectable auditory dysfunction, most particularly in young individuals, which raises the question on the origins of these more sporadic cases of phantom percept. In this issue of JAMA Otolaryngology–Head & Neck Surgery, Clifford et al1 present the first evidence in a genome-wide association study (GWAS) of 3 loci and 8 genes associated with tinnitus and replicated in 2 independent large cohorts of European ancestry: the UK Biobank and the Million Veterans Program. These findings go against the preconceived notion that tinnitus is purely a symptom and demonstrate that, at least in part, its neurological basis lies in the genes. A GWAS is the primary step in establishing the connection between genes and a trait by investigating the level of genetic variation between cases and controls. Thus, rather than looking at all the sequences from the entire genome, Clifford et al1 looked at specific sites across the whole genome, termed single-nucleotide variants (SNVs), where variations are expected to happen. A number of variants showed up consistently among individuals with tinnitus but not among those without tinnitus. Heritability of SNVs explained 6.3% of the variation; in other words, the identified SNVs explain nearly 6% of the trait. Including hearing difficulties as a covariate reduced tinnitus heritability by 18.8% to 35.6%, which reinforces the paradigm-shifting concept that not all tinnitus cases depend on hearing loss. With more than 1 gene being significantly associated with tinnitus, tinnitus can be defined as a polygenic disorder. Although these findings clearly demonstrate that tinnitus has a heritable component, they also indicate the importance of environmental factors in determining the full manifestation of tinnitus. Altogether, these features define tinnitus as a complex disorder, as opposed to rare mendelian disorders, wherein multiple genes and environmental factors interact together to generate a phenotype.
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Cederroth CR, Trpchevska N, Langguth B. A New Buzz for Tinnitus—It’s in the Genes! JAMA Otolaryngol Head Neck Surg. 2020;146(11):1025–1026. doi:10.1001/jamaoto.2020.2919
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