Converging evidence for shared genetic underpinnings of genetic generalized epilepsy and background EEG oscillations

Paroxysmal epileptiform abnormalities on EEG are the hallmark of epilepsies, but it is uncertain to what extent epilepsy and background EEG oscillations share neurobiological underpinnings. Confounding factors, including the heterogeneous etiology of epilepsies and medication effects hamper studies on background brain activity in people with epilepsy. To overcome this limitation, using genetic correlation, polygenic risk score (PRS), Mendelian Randomization and meta-analyses, we here provide consistent evidence for shared genetic underpinnings between genetic generalized epilepsy (GGE) and EEG beta power. Subjects in the highest 10% quantile of beta-power PRS scores are 1.4 fold more likely to suffer from GGE compared to the lowest 10% quantile. Moreover, we find increased enrichment of brain-expressed genes relative to the epilepsy and the EEG GWASs individually. In conclusion, our results point to shared biological mechanisms underlying background EEG and the susceptibility for seizures, opening avenues to investigate the clinical utility of beta oscillations in GGE.