ArticleCNS neuroscience & therapeutics2026
Shared Genetic Architecture Between Common Epilepsies and Subcortical Brain Volumes Is Associated With Cognition and Mental Health.
Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
aimsEpilepsy is a common neurological disorder, often presenting with psychiatric comorbidities and cognitive impairment. Neuroimaging studies have suggested associations between epilepsy and subcortical volumetric abnormalities. The genetic basis between epilepsy and subcortical volume abnormalities is, however, poorly understood, particularly if they share a common genetic architecture.
methodsTo investigate polygenic overlap, we employed the bivariate causal mixture model (MiXeR) to analyze genome-wide association data from various epilepsy subtypes (genetic generalized epilepsy [GGE]: n = 49,388, all epilepsy [EP]: n = 69,995, focal epilepsy: n = 57,375) and 16 subcortical volumetric phenotypes (n = 33,224). We identified shared genomic loci through conditional and conjunctional false discovery rate analyses (cond/conjFDR).
resultsMiXeR results suggest substantial shared genetic variants between subcortical volume and common epilepsies. ConjFDR analysis identified 33 distinct shared loci between GGE and subcortical volumetric phenotypes. The shared loci were mapped to 322 protein-coding genes. Among these, 49 genes showed significant expression-trait associations with both GGE and subcortical volume phenotypes, and 12 of the 322 genes were also associated with cognitive, mental health, and personality-related traits.
conclusionWe dissected the shared genetic architecture between common epilepsies and subcortical volumes. Expression-trait association analyses further identified candidate genes associated with cognitive, mental health, and personality-related phenotypes.
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