Genome-wide analysis implicates inner ear development in Ménière's disease.
Zhuozheng Shi1,2, Ravi Mandla1,2, Jingjing Li1
1Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Medrxiv : the Preprint Server for Health Sciences
|February 23, 2026
Summary
Ménière
Area of Science:
- Genetics
- Inner Ear Disorders
- Neuroscience
Background:
- Ménière's disease (MD) is a chronic inner ear condition with unknown causes.
- Symptoms include vertigo, hearing loss, and tinnitus.
- Understanding MD's genetic basis is crucial for diagnosis and treatment.
Purpose of the Study:
- To identify genetic loci associated with Ménière's disease risk.
- To explore the biological pathways contributing to MD pathogenesis.
- To investigate the genetic overlap between MD and related neurological and sensory disorders.
Main Methods:
- Genome-wide meta-analysis of over 8,900 MD cases and 1.9 million controls.
- Fine-mapping and integrative functional analyses of significant genetic loci.
- Phenome-wide and genetic correlation analyses with related traits.
Main Results:
- Identified five independent genome-wide significant loci for MD.
- Estimated SNP heritability at 7%, indicating a significant genetic contribution.
- Implicated inner ear developmental regulation (EYA4, EYA1, LMO4) and retinoic acid metabolism (CYP26A1/C1, ALDH1A2) pathways.
- Revealed shared genetic architecture with vertigo, hearing loss, migraine, and sleep apnea.
Conclusions:
- Established a genetic framework for Ménière's disease risk.
- Highlighted the role of developmental regulators and retinoic acid signaling in MD.
- Positioned MD within a broader spectrum of sensory and neurological disorders with shared genetic underpinnings.
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