Phenotypic heterogeneity in familial epilepsies is influenced by polygenic risk for generalized and focal epilepsies

Abstract

Objective: Although previous research shows that generalized and focal epilepsies have at least some distinct genetic influences, it remains uncertain why some families manifest both types of epilepsy. We tested two hypotheses: (1) families with both generalized and focal epilepsy carry separate risk alleles for both types; and (2) within mixed families, the type of epilepsy each individual manifests is influenced by the relative burden of separate risk alleles for generalized epilepsies and focal epilepsies. Methods: The Epi4K cohort included 711 individuals with epilepsy from 257 families (113 generalized families, 66 focal families, 78 mixed families). We calculated polygenic risk scores ..