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Article: Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations

TitleShared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations
Authors
Advisors
Issue Date2021
PublisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.epilepsia.com/
Citation
Epilepsia, 2021, v. 62 n. 7, p. 1518-1527 How to Cite?
AbstractObjective: 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.
DescriptionHybrid open access; Research Grants Council of the Hong Kong Special Administrative Region, China project numbers HKU7623/08 M (Stacey S. Cherny, Patrick Kwan, Larry Baum, Pak C. Sham), HKU7747/ 07 M (Stacey S. Cherny., Pak C. Sham), and CUHK4466/06 M (Patrick Kwan, Larry Baum)
Persistent Identifierhttp://hdl.handle.net/10722/303999
ISSN
2023 Impact Factor: 6.6
2023 SCImago Journal Rankings: 2.227
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.advisorBaum, LW-
dc.contributor.advisorCherny, SS-
dc.contributor.advisorSham, PC-
dc.contributor.authorStevelink, R-
dc.contributor.authorLuykx, JJ-
dc.contributor.authorLin, BD-
dc.contributor.authorLeu, C-
dc.contributor.authorLal, D-
dc.contributor.authorSmith, AW-
dc.contributor.authorSchijven, D-
dc.contributor.authorCarpay, JA-
dc.contributor.authorRademaker, K-
dc.contributor.authorBaldez, RAR-
dc.contributor.authorDevinsky, O-
dc.contributor.authorBraun, KPJ-
dc.contributor.authorJansen, FE-
dc.contributor.authorSmit, DJA-
dc.contributor.authorKoeleman, BPC-
dc.contributor.authorInternational League Against Epilepsy Consortium on Complex Epilepsies-
dc.contributor.authorEpi25 Collaborative-
dc.date.accessioned2021-09-23T08:53:49Z-
dc.date.available2021-09-23T08:53:49Z-
dc.date.issued2021-
dc.identifier.citationEpilepsia, 2021, v. 62 n. 7, p. 1518-1527-
dc.identifier.issn0013-9580-
dc.identifier.urihttp://hdl.handle.net/10722/303999-
dc.descriptionHybrid open access; Research Grants Council of the Hong Kong Special Administrative Region, China project numbers HKU7623/08 M (Stacey S. Cherny, Patrick Kwan, Larry Baum, Pak C. Sham), HKU7747/ 07 M (Stacey S. Cherny., Pak C. Sham), and CUHK4466/06 M (Patrick Kwan, Larry Baum)-
dc.description.abstractObjective: 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.-
dc.languageeng-
dc.publisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.epilepsia.com/-
dc.relation.ispartofEpilepsia-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleShared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations-
dc.typeArticle-
dc.identifier.emailBaum, LW: lwbaum@hku.hk-
dc.identifier.emailCherny, SS: cherny@hku.hk-
dc.identifier.emailSham, PC: pcsham@hku.hk-
dc.identifier.authorityCherny, SS=rp00232-
dc.identifier.authoritySham, PC=rp00459-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1111/epi.16922-
dc.identifier.pmid34002374-
dc.identifier.scopuseid_2-s2.0-85106288759-
dc.identifier.hkuros324949-
dc.identifier.volume62-
dc.identifier.issue7-
dc.identifier.spage1518-
dc.identifier.epage1527-
dc.identifier.isiWOS:000651408300001-
dc.publisher.placeUnited States-

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