TUESDAY, July 7, 2026 (HealthDay News) -- Five independent genome-wide significant loci have been identified for Meniere disease (MD) risk, implicating convergent biological processes, according to a study published in the July 2 issue of the American Journal of Human Genetics.
Zhuozheng Shi, from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues conducted a genome-wide meta-analysis of 8,969 MD cases and 1,962,542 controls across five biobanks to explore the etiology of MD.
The researchers identified five independent genome-wide significant loci, estimating an observed-scale single nucleotide polymorphism heritability of 7 percent. Two independent variants at EYA4, two at EYA1, and one near CYP26A1 had genome-wide significant signals, with odds ratios between 1.10 and 1.25. Associations at LMO4 and ALDH1A2 fell just below the threshold for genome-wide significance. Two convergent biological processes were implicated by fine-mapping and integrative functional analyses: developmental regulation of the inner ear, which involved EYA4, EYA1, and LMO4, and retinoic acid metabolism, with associations near CYP26A1/C1 and ALDH1A2. Fetal and adult human inner ear cell types robustly express these developmental regulator genes. Shared genetic architecture between MD and related traits was further revealed on phenome-wide and genetic correlation analyses.
"This is an important step forward, but it's still early," senior author Iain Mathieson, Ph.D., also from the University of Pennsylvania, said in a statement. "What we've done is map out where to look. The next challenge is to understand exactly how the genes we've identified affect the inner ear and whether that knowledge can eventually lead to better treatments."
