Vestibular migraine as a vestibulo-trigeminal interface phenotype: a triangulation study across genetics, peripheral multiomics and human cell atlases
Abstract
Abstract Background Vestibular migraine (VM) is clinically established, but the biological problem is narrower and harder: whether VM has its own causal architecture or instead reflects migraine liability that is preferentially expressed through vestibular systems. We tested the latter possibility by asking whether migraine-vertigo overlap converges on vestibular and trigeminal programs. Methods We used four evidence layers: population-scale migraine-related and vertigo-related GWAS summary statistics, with FinnGen as the primary backbone; an independent external vertigo GWAS meta-analysis for supportive anchoring; disease-labeled peripheral blood transcriptomic and multiomic datasets spanning VM, migraine, Meniere disease, and healthy controls; and human trigeminal ganglion and vestibular or inner-ear single-cell atlases for biological localization. We quantified genome-wide and local migraine-vertigo overlap, prioritized shared-liability loci and genes, and then asked whether downstream layers supported the same signal. Results Migraine-related and vertigo-related phenotypes showed strong genome-wide genetic correlation, including overall migraine versus vertigo (rg = 0.5277, SE = 0.0525, p = 9.18 x 10^-24), migraine with aura versus vertigo (rg = 0.5698, SE = 0.0734, p = 8.61 x 10^-15), and migraine without aura versus vertigo (rg = 0.4710, SE = 0.0615, p = 1.90 x 10^-14). Local analyses identified 8 shared blocks, and shared-liability prioritization yielded 204 candidate…
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