OBJECTIVE: Paroxysmal epileptiform abnormalities on electroencephalography (EEG) are the hallmark of epilepsies, but it is uncertain to what extent epilepsy and background EEG oscillations share neurobiological underpinnings. Here, we aimed to assess the genetic correlation between epilepsy and background EEG oscillations. METHODS: 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, we compared genetic data from a genome-wide association study (GWAS) on epilepsy (n = 12 803 people with epilepsy and 24 218 controls) with that from a GWAS on background EEG (n = 8425 subjects without epilepsy), in which background EEG oscillation power was quantified in four different frequency bands: alpha, beta, delta, and theta. We replicated our findings in an independent epilepsy replication dataset (n = 4851 people with epilepsy and 20 428 controls). To assess the genetic overlap between these phenotypes, we performed genetic correlation analyses using linkage disequilibrium score regression, polygenic risk scores, and Mendelian randomization analyses. RESULTS: Our analyses show strong genetic correlations of genetic generalized epilepsy (GGE) with background EEG oscillations, primarily in the beta frequency band. Furthermore, we show that subjects with higher beta and theta polygenic risk scores have a significantly higher risk of having generalized epilepsy. Mendelian randomization analyses suggest a causal effect of GGE genetic liability on beta oscillations. SIGNIFICANCE: Our results point to shared biological mechanisms underlying background EEG oscillations and the susceptibility for GGE, opening avenues to investigate the clinical utility of background EEG oscillations in the diagnostic workup of epilepsy.
FörderungenChildren's Hospital of Philadelphia Royal Melbourne Hospital Foundation National Hospital for Neurology and Neurosurgery Ming Fund GIHE Fondation Erasme EuroEPINOMICS Consortium Department of Health NIHR Biomedical Research Centres European Commission Wellcome Trust Health Research Board, Ireland Royal Melbourne Hospital Neuroscience Foundation UCL Institute of Neurology, University College London National Health and Medical Research Council (NHMRC) Bundesministerium fur Bildung und Forschung (BMBF) Ludwig-Maximilians-Universitat Munchen Fonds De La Recherche Scientifique - FNRS Université Libre de Bruxelles European Regional Development Fund (ERDF) Deutsches Forschungszentrum für Gesundheit und Umwelt, Helmholtz Zentrum München Münchner Zentrum für Gesundheitswissenschaften, Ludwig-Maximilians-Universität München Epilepsy Society