Article (Scientific journals)
Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations
Stevelink, Remi; Luykx, Jurjen J.; Lin, Bochao D. et al.
2021In Epilepsia, 62 (7), p. 1518-1527
Peer reviewed
 

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Keywords :
beta power; EEG; generalized epilepsy; GGE; oscillations; PRS
Abstract :
[en] Abstract 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.
Disciplines :
Genetics & genetic processes
Neurology
Author, co-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.
International League Against Epilepsy Consortium On ComplexEpilepsies
Epi25 Collaborative
MAY, Patrick  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
KRAUSE, Roland  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
More authors (9 more) Less
External co-authors :
yes
Language :
English
Title :
Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations
Publication date :
18 May 2021
Journal title :
Epilepsia
Volume :
62
Issue :
7
Pages :
1518-1527
Peer reviewed :
Peer reviewed
Focus Area :
Systems Biomedicine
Available on ORBilu :
since 08 December 2021

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