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Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations
Epilepsia, Volume: 62, Issue: 7, Pages: 1518 - 1527
Swansea University Author: Robert Powell
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DOI (Published version): 10.1111/epi.16922
Abstract
ObjectiveParoxysmal 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 backgr...
Published in: | Epilepsia |
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ISSN: | 0013-9580 1528-1167 |
Published: |
Wiley
2021
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Online Access: |
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URI: | https://cronfa.swan.ac.uk/Record/cronfa60623 |
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Abstract: |
ObjectiveParoxysmal 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.MethodsConfounding 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.ResultsOur 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.SignificanceOur 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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Keywords: |
beta power, EEG, generalized epilepsy, GGE, oscillations, PRS |
College: |
Faculty of Medicine, Health and Life Sciences |
Funders: |
Science Foundation Ireland. Grant Numbers: 16/RC/3948, 13/CDA/2223; European Regional Development Fund; FutureNeuro industry partners; Wellcome Trust. Grant Numbers: 084730, WT066056; Epilepsy Society, UK, NIHR. Grant Number: 08-08-SCC; GIHE. Grant Numbers: NIH R01-NS-49306-01, NIH R01-NS-053998; GSCFE. Grant Number: NIH R01-NS-064154-01; NIH. Grant Number: UL1TR001070; The Children’s Hospital of Philadelphia; NHMRC. Grant Number: 1091593; The Royal Melbourne Hospital Foundation Lottery Grant; The RMH Neuroscience Foundation; European Union’s Seventh Framework Programme (FP7/2007-2013). Grant Number: 279062; Department of Health’s NIHR Biomedical Research Centers funding scheme, European Community. Grant Number: LSHM-CT2006-037315; German Research Foundation. Grant Number: SA434/4-1/4-26-1; European Science Foundation. Grant Numbers: SA434/5-1, NU50/8-1, LE1030/11-1, HE5415/3-1, RO 3396/2-1; German Federal Ministry of Education and Research, National Genome Research Network. Grant Numbers: 01GS08120, 01GS08123; The Netherlands National Epilepsy Fund. Grant Number: 04-08; Research Grants Council of the Hong Kong Special Administrative Region. Grant Numbers: HKU7623/08 M, HKU7747/ 07 M, CUHK4466/06 M; Fonds National de la Recherche Scientifique; Fondation Erasme; Université Libre de Bruxelles; NIHR Biomedical Research Centres Schem. Grant Number: P31753; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Grant Number: N01HD33348; German Ministry for Education and Research. Grant Number: 01EY1103; Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria; Helmholtz Zentrum München–German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research and by the State of Bavaria; Munich Center of Health Sciences; Ludwig Maximilian University, as part of LMUinnovativ |
Issue: |
7 |
Start Page: |
1518 |
End Page: |
1527 |