2023 NHCA Annual Conference

Tinnitus, a phantom perception of sound in the absence of any external sound source, is an etiologically heterogenous trait linked to occupational and recreational noise exposure. Recent studies highlighted a polygenic architecture of genetic susceptibility to tinnitus. Tinnitus is frequently accompanied by neuropsychiatric comorbidities (such as anxiety and depression). However, shared genetic underpinnings between tinnitus and psychiatric conditions remain elusive. We performed a genome-wide association study of tinnitus and tinnitus-related distress using the UK Biobank database (N=132,438), followed by tissue and trait-specific enrichment analyses. We identified a locus in the vicinity of GPM6A achieving genome-wide significance (p<5E-8). Nineteen independent loci reach suggestive association (p<E-6). The enrichment analysis identified a shared genetic component between tinnitus and neuropsychiatric traits (such as bipolar disorder, cognitive ability, fast beta electroencephalogram, and sensation seeking). Tissue-specific enrichment analysis showed that the GWAS signals were collectively enriched in the hippocampus and cortex. This study provides novel insights into the genetic processes underlying tinnitus and demonstrated a shared genetic component underlying tinnitus and neuropsychiatric conditions.