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Stevelink, R.* ; Luykx, J.J.* ; Lin, B.D.* ; Leu, C.* ; Lal, D.* ; Smith, A.W.* ; Schijven, D.* ; Carpay, J.A.* ; Rademaker, K.* ; Rodrigues Baldez, R.A.* ; Devinsky, O.* ; Braun, K.P.J.* ; Jansen, F.E.* ; Smit, D.J.A.* ; Koeleman, B.P.C.* ; The International League Against Epilepsy Consortium on Complex Epilepsies (Gieger, C.) ; The International League Against Epilepsy Consortium on Complex Epilepsies (Strauch, K.)

Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations.

Epilepsia 62, 1518-1527 (2021)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Eeg ; Gge ; Prs ; Beta Power ; Generalized Epilepsy ; Oscillations
ISSN (print) / ISBN 0013-9580
e-ISSN 1528-1167
Journal Epilepsia
Quellenangaben Volume: 62, Issue: 7, Pages: 1518-1527 Article Number: , Supplement: ,
Publisher Wiley
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)
Grants Children'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