A genome-wide association study (GWAS) was done in patients with idiopathic bilateral vestibulopathy (BVP) to identify underlying genetic causes.

We analyzed a European cohort of 132 individuals diagnosed with idiopathic BVP and 3,410 unaffected controls. Demographic and clinical data were collected from affected individuals.  Diagnosis was based on the current diagnostic criteria of the Bárány Society. Following quality control and removal of outliers, genome-wide association was performed on approximately 7.5 million variants, complemented by gene-based analysis with MAGMA.

GWAS identified two loci reaching genome-wide significance. The strongest signal mapped to chromosome 19 (ZNF91/LINC01224), with rs12185481 (p = 3.60E-16) as the lead variant. A second, more tentative signal emerged on chromosome 2 represented by rs73006457 (p = 4.46E-08) with GPC1 and OTOS as the nearest candidate genes. Gene-based analysis revealed six significant loci, including ZNF91, highlighting novel candidate genes with potential relevance to BVP pathogenesis.

This study provides novel insights into the genetic basis of previously idiopathic BVP, pointing to ZNF91/LINC01224 as a major contributor. The association of this locus suggests a functional link between transcriptional regulation, retrotransposon silencing, and vestibular pathology with age-related decline in ZNF91 expression potentially amplifying genetic risk and aligning with the typical mid-to late-adult onset of BVP. The second locus near OTOS on chromosome 2 represents a less robust, though pathophysiologically plausible candidate, as OTOS is expressed in the inner ear and has previously been associated with susceptibility to ototoxic-induced hearing loss. Together, these findings highlight novel pathways in BVP pathogenesis and merit replication in larger, independent cohorts.