期刊
EPILEPSIA
卷 62, 期 7, 页码 1518-1527出版社
WILEY
DOI: 10.1111/epi.16922
关键词
beta power; EEG; generalized epilepsy; GGE; oscillations; PRS
资金
- Science Foundation Ireland [16/RC/3948, 13/CDA/2223]
- European Regional Development Fund
- FutureNeuro industry partners
- Wellcome Trust [084730, WT066056]
- Epilepsy Society, UK, NIHR [08-08-SCC]
- GIHE [NIH R01-NS-49306-01, NIH R01-NS-053998]
- GSCFE [NIH R01-NS-064154-01]
- NIH [UL1TR001070]
- Children's Hospital of Philadelphia
- NHMRC [1091593]
- Royal Melbourne Hospital Foundation Lottery Grant
- RMH Neuroscience Foundation
- European Union's Seventh Framework Programme (FP7/2007-2013) [279062]
- Department of Health's NIHR Biomedical Research Centers funding scheme, European Community [LSHM-CT2006-037315]
- German Research Foundation [SA434/4-1/4-26-1]
- European Science Foundation [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 [01GS08120, 01GS08123]
- Netherlands National Epilepsy Fund [04-08]
- Research Grants Council of the Hong Kong Special Administrative Region [HKU7623/08 M, HKU7747/07 M, CUHK4466/06 M]
- Fonds National de la Recherche Scientifique
- Fondation Erasme
- Universite Libre de Bruxelles
- NIHR Biomedical Research Centres Schem [P31753]
- Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development [N01HD33348]
- German Ministry for Education and Research [01EY1103]
- Helmholtz Zentrum Munchen - German Research Center for Environmental Health - German Federal Ministry of Education and Research (BMBF)
- State of Bavaria
- Helmholtz Zentrum Munchen-German Research Center for Environmental Health - German Federal Ministry of Education and Research
- Munich Center of Health Sciences
- Ludwig Maximilian University, as part of LMUinnovativ
- Science Foundation Ireland (SFI) [13/CDA/2223] Funding Source: Science Foundation Ireland (SFI)
The study found a strong genetic correlation between genetic generalized epilepsy (GGE) and background EEG oscillations, particularly in the beta frequency band. Individuals with higher beta and theta polygenic risk scores have a significantly increased risk of generalized epilepsy. Mendelian randomization analyses suggest a causal effect of GGE genetic liability on beta oscillations.
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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