Genome-wide analysis implicates inner ear development in Ménière disease.

Common susceptibility loci implicating inner-ear development (EYA4, EYA1, LMO4) and retinoic acid metabolism (CYP26A1, ALDH1A2)

Ménière disease, a chronic inner-ear disorder (recurrent vertigo, fluctuating sensorineural hearing loss, tinnitus), remains poorly understood. This genome-wide meta-analysis (8,969 cases, ~1.96 million controls, five biobanks) identifies five significant loci — two variants at EYA4, two at EYA1, one near CYP26A1 — with an observed-scale SNP heritability of ~7%. Fine-mapping and functional analyses converge on two processes: developmental regulation of the inner ear (EYA4, EYA1, LMO4) and retinoic acid metabolism (CYP26A1, ALDH1A2). These genes are strongly expressed in fetal and adult inner-ear cell types.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A first robust genetic signal in a poorly understood disorder, with a coherent pathophysiological lead (inner-ear development, retinoic acid signalling). Clinical impact remains distant — modest ORs (1.1–1.25) and limited common heritability — but the value is mainly mechanistic and aetiological, with no immediate diagnostic application.

Analysis by Dr Thibaut Benquey