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Shared genetic basis between genetic generalized epilepsy and background electroencephalographic 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 back...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672363/ https://www.ncbi.nlm.nih.gov/pubmed/34002374 http://dx.doi.org/10.1111/epi.16922 |
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author | Stevelink, Remi Luykx, Jurjen J. Lin, Bochao D. Leu, Costin Lal, Dennis Smith, Alexander W. Schijven, Dick Carpay, Johannes A. Rademaker, Koen Rodrigues Baldez, Roiza A. Devinsky, Orrin Braun, Kees P. J. Jansen, Floor E. Smit, Dirk J. A. Koeleman, Bobby P. C. |
author_facet | Stevelink, Remi Luykx, Jurjen J. Lin, Bochao D. Leu, Costin Lal, Dennis Smith, Alexander W. Schijven, Dick Carpay, Johannes A. Rademaker, Koen Rodrigues Baldez, Roiza A. Devinsky, Orrin Braun, Kees P. J. Jansen, Floor E. Smit, Dirk J. A. Koeleman, Bobby P. C. |
author_sort | Stevelink, Remi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8672363 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86723632021-12-22 Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations Stevelink, Remi Luykx, Jurjen J. Lin, Bochao D. Leu, Costin Lal, Dennis Smith, Alexander W. Schijven, Dick Carpay, Johannes A. Rademaker, Koen Rodrigues Baldez, Roiza A. Devinsky, Orrin Braun, Kees P. J. Jansen, Floor E. Smit, Dirk J. A. Koeleman, Bobby P. C. Epilepsia Full‐length Original Research 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. John Wiley and Sons Inc. 2021-05-18 2021-07 /pmc/articles/PMC8672363/ /pubmed/34002374 http://dx.doi.org/10.1111/epi.16922 Text en © 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Full‐length Original Research Stevelink, Remi Luykx, Jurjen J. Lin, Bochao D. Leu, Costin Lal, Dennis Smith, Alexander W. Schijven, Dick Carpay, Johannes A. Rademaker, Koen Rodrigues Baldez, Roiza A. Devinsky, Orrin Braun, Kees P. J. Jansen, Floor E. Smit, Dirk J. A. Koeleman, Bobby P. C. Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations |
title | Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations |
title_full | Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations |
title_fullStr | Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations |
title_full_unstemmed | Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations |
title_short | Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations |
title_sort | shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations |
topic | Full‐length Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672363/ https://www.ncbi.nlm.nih.gov/pubmed/34002374 http://dx.doi.org/10.1111/epi.16922 |
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