Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations. (18th May 2021)

• Record Type: Journal Article
• Authors: 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.
• Other Names: Abou‐Khalil Bassel investigator.; Auce Pauls investigator.; Avbersek Andreja investigator.; Bahlo Melanie investigator.; Balding David J. investigator.; Bast Thomas investigator.; Baum Larry investigator.; Becker Albert J. investigator.; Becker Felicitas investigator.; Berghuis Bianca investigator.; Berkovic Samuel F. investigator.; Boysen Katja E. investigator.; Bradfield Jonathan P. investigator.; Brody Lawrence C. investigator.; Buono Russell J. investigator.; Campbell Ellen investigator.; Cascino Gregory D. investigator.; Catarino Claudia B. investigator.; Cavalleri Gianpiero L. investigator.; Cherny Stacey S. investigator.; Chinthapalli Krishna investigator.; Coffey Alison J. investigator.; Compston Alastair investigator.; Coppola Antonietta investigator.; Cossette Patrick investigator.; Craig John J. investigator.; de Haan Gerrit‐Jan investigator.; De Jonghe Peter investigator.; de Kovel Carolien G. F. investigator.; Delanty Norman investigator.; Depondt Chantal investigator.; Dlugos Dennis J. investigator.; Doherty Colin P. investigator.; Elger Christian E. investigator.; Eriksson Johan G. investigator.; Ferraro Thomas N. investigator.; Feucht Martha investigator.; Francis Ben investigator.; Franke Andre investigator.; French Jacqueline A. investigator.; Freytag Saskia investigator.; Gaus Verena investigator.; Geller Eric B. investigator.; Gieger Christian investigator.; Glauser Tracy investigator.; Glynn Simon investigator.; Goldstein David B. investigator.; Gui Hongsheng investigator.; Guo Youling investigator.; Haas Kevin F. investigator.; Hakonarson Hakon investigator.; Hallmann Kerstin investigator.; Haut Sheryl investigator.; Heinzen Erin L. investigator.; Helbig Ingo investigator.; Hengsbach Christian investigator.; Hjalgrim Helle investigator.; Iacomino Michele investigator.; Ingason Andrés investigator.; Jamnadas‐Khoda Jennifer investigator.; Johnson Michael R. investigator.; Kälviäinen Reetta investigator.; Kantanen Anne‐Mari investigator.; Kasperavičiūte Dalia investigator.; Kasteleijn‐Nolst Trenite Dorothee investigator.; Kirsch Heidi E. investigator.; Knowlton Robert C. investigator.; Krause Roland investigator.; Krenn Martin investigator.; Kunz Wolfram S. investigator.; Kuzniecky Ruben investigator.; Kwan Patrick investigator.; Lau Yu‐Lung investigator.; Lehesjoki Anna‐Elina investigator.; Lerche Holger investigator.; Lieb Wolfgang investigator.; Lindhout Dick investigator.; Lo Warren D. investigator.; Lopes‐Cendes Iscia investigator.; Lowenstein Daniel H. investigator.; Malovini Alberto investigator.; Marson Anthony G. investigator.; Mayer Thomas investigator.; McCormack Mark investigator.; Mills James L. investigator.; Mirza Nasir investigator.; Moerzinger Martina investigator.; Møller Rikke S. investigator.; Molloy Anne M. investigator.; Muhle Hiltrud investigator.; Newton Mark investigator.; Ng Ping‐Wing investigator.; Nöthen Markus M. investigator.; Nürnberg Peter investigator.; O'Brien Terence J. investigator.; Oliver Karen L. investigator.; Palotie Aarno investigator.; Pangilinan Faith investigator.; Peter Sarah investigator.; Petrovski Slavé investigator.; Poduri Annapurna investigator.; Privitera Michael investigator.; Radtke Rodney investigator.; Rau Sarah investigator.; Reif Philipp S. investigator.; Reinthaler Eva M. investigator.; Rosenow Felix investigator.; Sander Josemir W. investigator.; Sander Thomas investigator.; Scattergood Theresa investigator.; Schachter Steven C. investigator.; Schankin Christoph J. investigator.; Scheffer Ingrid E. investigator.; Schmitz Bettina investigator.; Schoch Susanne investigator.; Sham Pak C. investigator.; Shih Jerry J. investigator.; Sills Graeme J. investigator.; Sisodiya Sanjay M. investigator.; Slattery Lisa investigator.; Smith David F. investigator.; Smith Michael C. investigator.; Smith Philip E. investigator.; Sonsma Anja C. M. investigator.; Speed Doug investigator.; Sperling Michael R. investigator.; Steinhoff Bernhard J. investigator.; Stephani Ulrich investigator.; Strauch Konstantin investigator.; Striano Pasquale investigator.; Stroink Hans investigator.; Surges Rainer investigator.; Tan K. Meng investigator.; Thio Liu Lin investigator.; Thomas G. Neil investigator.; Todaro Marian investigator.; Tozzi Rossana investigator.; Vari Maria S. investigator.; Vining Eileen P. 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Cotsapas Chris investigator.; De Jonghe Peter investigator.; Dixon‐Salazar Tracy investigator.; Guerrini Renzo investigator.; Hakonarson Hakon investigator.; Heinzen Erin L. investigator.; Helbig Ingo investigator.; Kwan Patrick investigator.; Petrovski Slavé investigator.; Kamalakaran Sitharthan investigator.; Sisodiya Sanjay M. investigator.; Stewart Randy investigator.; Weckhuysen Sarah investigator.; Dlugos Dennis J. investigator.; Scheffer Ingrid E. investigator.; Striano Pasquale investigator.; Freyer Catharine investigator.; Krause Roland investigator.; May Patrick investigator.; McKenna Kevin investigator.; Regan Brigid M. investigator.; Bellows Susannah T. investigator.; Bennett Caitlin A. investigator.; Johns Esther M.C. investigator.; Macdonald Alexandra investigator.; Shilling Hannah investigator.; Burgess Rosemary investigator.; Weckhuysen Dorien investigator.; Bahlo Melanie investigator.; O'Brien Terence J. investigator.; Todaro Marian investigator.; Stamberger Hannah investigator.; 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Schneider Natascha investigator.; Balestrini Simona investigator.; Zagaglia Sara investigator.; Braatz Vera investigator.; Marson Anthony G. investigator.; Johnson Michael R. investigator.; Auce Pauls investigator.; Sills Graeme J. investigator.; Baum Larry W. investigator.; Sham Pak C. investigator.; Cherny Stacey S. investigator.; Lui Colin H.T. investigator.; Barišić Nina investigator.; Delanty Norman investigator.; Doherty Colin P. investigator.; Shukralla Arif investigator.; McCormack Mark investigator.; El‐Naggar Hany investigator.; Canafoglia Laura investigator.; Franceschetti Silvana investigator.; Castellotti Barbara investigator.; Granata Tiziana investigator.; Zara Federico investigator.; Iacomino Michele investigator.; Madia Francesca investigator.; Stella Vari Maria investigator.; Mancardi Maria Margherita investigator.; Salpietro Vincenzo investigator.; Bisulli Francesca investigator.; Tinuper Paolo investigator.; Licchetta Laura investigator.; Pippucci Tommaso investigator.; 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• Is Part Of: Epilepsia. Volume 62:issue 7(2021)
• Page Start: 1518
• Page End: 1527
• Publication Date: 2021-05-18
• Subjects: beta power -- EEG -- generalized epilepsy -- GGE -- oscillations -- PRS; Epilepsy -- Periodicals; 616.853
• DOI: 10.1111/epi.16922
• Languages: English
• ISSNs: 0013-9580

Abstract

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.