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Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations

Remi Stevelink Orcid Logo, Jurjen J. Luykx, Bochao D. Lin, Costin Leu, Dennis Lal, Alexander W. Smith, Dick Schijven, Johannes A. Carpay, Koen Rademaker, Roiza A. Rodrigues Baldez, Orrin Devinsky Orcid Logo, Kees P. J. Braun, Floor E. Jansen, Dirk J. A. Smit, Bobby P. C. Koeleman, Bassel Abou‐Khalil, Pauls Auce, Andreja Avbersek, Melanie Bahlo, David J. Balding, Thomas Bast, Larry Baum, Albert J. Becker, Felicitas Becker, Bianca Berghuis, Samuel F. Berkovic, Katja E. Boysen, Jonathan P. Bradfield, Lawrence C. Brody, Russell J. Buono, Ellen Campbell, Gregory D. Cascino, Claudia B. Catarino, Gianpiero L. Cavalleri, Stacey S. Cherny, Krishna Chinthapalli, Alison J. Coffey, Alastair Compston, Antonietta Coppola, Patrick Cossette, John J. Craig, Gerrit‐Jan Haan, Peter De Jonghe, Carolien G. F. Kovel, Norman Delanty, Chantal Depondt, Dennis J. Dlugos, Colin P. Doherty, Christian E. Elger, Johan G. Eriksson, Thomas N. Ferraro, Martha Feucht, Ben Francis, Andre Franke, Jacqueline A. French, Saskia Freytag, Verena Gaus, Eric B. Geller, Christian Gieger, Tracy Glauser, Simon Glynn, David B. Goldstein, Hongsheng Gui, Youling Guo, Kevin F. Haas, Hakon Hakonarson, Kerstin Hallmann, Sheryl Haut, Erin L. Heinzen, Ingo Helbig, Christian Hengsbach, Helle Hjalgrim, Michele Iacomino, Andrés Ingason, Jennifer Jamnadas‐Khoda, Michael R. Johnson, Reetta Kälviäinen, Anne‐Mari Kantanen, Dalia Kasperavičiūte, Dorothee Kasteleijn‐Nolst Trenite, Heidi E. Kirsch, Robert C. Knowlton, Roland Krause, Martin Krenn, Wolfram S. Kunz, Ruben Kuzniecky, Patrick Kwan, Yu‐Lung Lau, Anna‐Elina Lehesjoki, Holger Lerche, Wolfgang Lieb, Dick Lindhout, Warren D. Lo, Iscia Lopes‐Cendes, Daniel H. Lowenstein, Alberto Malovini, Anthony G. Marson, Thomas Mayer, Mark McCormack, James L. Mills, Nasir Mirza, Martina Moerzinger, Rikke S. Møller, Anne M. Molloy, Hiltrud Muhle, Mark Newton, Ping‐Wing Ng, Markus M. Nöthen, Peter Nürnberg, Terence J. O’Brien, Karen L. Oliver, Aarno Palotie, Faith Pangilinan, Sarah Peter, Slavé Petrovski, Annapurna Poduri, Michael Privitera, Rodney Radtke, Sarah Rau, Philipp S. Reif, Eva M. Reinthaler, Felix Rosenow, Josemir W. Sander, Thomas Sander, Theresa Scattergood, Steven C. Schachter, Christoph J. Schankin, Ingrid E. Scheffer, Bettina Schmitz, Susanne Schoch, Pak C. Sham, Jerry J. Shih, Graeme J. Sills, Sanjay M. Sisodiya, Lisa Slattery, David F. Smith, Michael C. Smith, Philip E. Smith, Anja C. M. Sonsma, Doug Speed, Michael R. Sperling, Bernhard J. Steinhoff, Ulrich Stephani, Konstantin Strauch, Pasquale Striano, Hans Stroink, Rainer Surges, K. Meng Tan, Liu Lin Thio, G. Neil Thomas, Marian Todaro, Rossana Tozzi, Maria S. Vari, Eileen P. G. Vining, Frank Visscher, Sarah Spiczak, Nicole M. Walley, Yvonne G. Weber, Zhi Wei, Ruta Mameniskiene, Judith Weisenberg, Christopher D. Whelan, Peter Widdess‐Walsh, Markus Wolff, Stefan Wolking, Wanling Yang, Federico Zara, Fritz Zimprich, Yen‐Chen Anne Feng, Daniel P. Howrigan, Liam E. Abbott, Katherine Tashman, Felecia Cerrato, Dennis Lal, Claire Churchhouse, Namrata Gupta, Stacey B. Gabriel, Mark J. Daly, Eric S. Lander, Benjamin M. Neale, Samuel F. Berkovic, Holger Lerche, David B. Goldstein, Daniel H. Lowenstein, Gianpiero L. Cavalleri, Patrick Cossette, Chris Cotsapas, Peter De Jonghe, Tracy Dixon‐Salazar, Renzo Guerrini, Hakon Hakonarson, Erin L. Heinzen, Ingo Helbig, Patrick Kwan, Slavé Petrovski, Sitharthan Kamalakaran, Sanjay M. Sisodiya, Randy Stewart, Sarah Weckhuysen, Dennis J. Dlugos, Ingrid E. Scheffer, Pasquale Striano, Catharine Freyer, Roland Krause, Patrick May, Kevin McKenna, Brigid M. Regan, Susannah T. Bellows, Caitlin A. Bennett, Esther M.C. Johns, Alexandra Macdonald, Hannah Shilling, Rosemary Burgess, Dorien Weckhuysen, Melanie Bahlo, Terence J. O'Brien, Marian Todaro, Hannah Stamberger, Chantal Depondt, Danielle M. Andrade, Tara R. Sadoway, Kelly Mo, Heinz Krestel, Sabina Gallati, Savvas S. Papacostas, Ioanna Kousiappa, George A. Tanteles, Katalin Štěrbová, Markéta Vlčková, Lucie Sedláčková, Petra Laššuthová, Karl Martin Klein, Felix Rosenow, Philipp S. Reif, Susanne Knake, Wolfram S. Kunz, Gábor Zsurka, Christian E. Elger, Jürgen Bauer, Michael Rademacher, Manuela Pendziwiat, Hiltrud Muhle, Annika Rademacher, Andreas Baalen, Sarah Spiczak, Ulrich Stephani, Zaid Afawi, Amos D. Korczyn, Moien Kanaan, Christina Canavati, Gerhard Kurlemann, Karen Müller‐Schlüter, Gerhard Kluger, Martin Häusler, Ilan Blatt, Johannes R. Lemke, Ilona Krey, Yvonne G. Weber, Stefan Wolking, Felicitas Becker, Christian Hengsbach, Sarah Rau, Ana F. Maisch, Bernhard J. Steinhoff, Andreas Schulze‐Bonhage, Susanne Schubert‐Bast, Herbert Schreiber, Ingo Borggräfe, Christoph J. Schankin, Thomas Mayer, Rudolf Korinthenberg, Knut Brockmann, Dieter Dennig, Rene Madeleyn, Reetta Kälviäinen, Pia Auvinen, Anni Saarela, Tarja Linnankivi, Anna‐Elina Lehesjoki, Mark I. Rees, Seo‐Kyung Chung, William O. Pickrell, Robert Powell, Natascha Schneider, Simona Balestrini, Sara Zagaglia, Vera Braatz, Anthony G. Marson, Michael R. Johnson, Pauls Auce, Graeme J. Sills, Larry W. Baum, Pak C. Sham, Stacey S. Cherny, Colin H.T. Lui, Nina Barišić, Norman Delanty, Colin P. Doherty, Arif Shukralla, Mark McCormack, Hany El‐Naggar, Laura Canafoglia, Silvana Franceschetti, Barbara Castellotti, Tiziana Granata, Federico Zara, Michele Iacomino, Francesca Madia, Maria Stella Vari, Maria Margherita Mancardi, Vincenzo Salpietro, Francesca Bisulli, Paolo Tinuper, Laura Licchetta, Tommaso Pippucci, Carlotta Stipa, Raffaella Minardi, Antonio Gambardella, Angelo Labate, Grazia Annesi, Lorella Manna, Monica Gagliardi, Elena Parrini, Davide Mei, Annalisa Vetro, Claudia Bianchini, Martino Montomoli, Viola Doccini, Carla Marini, Toshimitsu Suzuki, Yushi Inoue, Kazuhiro Yamakawa, Birute Tumiene, Lynette G. Sadleir, Chontelle King, Emily Mountier, S. Hande Caglayan, Mutluay Arslan, Zuhal Yapıcı, Uluc Yis, Pınar Topaloglu, Bulent Kara, Dilsad Turkdogan, Aslı Gundogdu‐Eken, Nerses Bebek, Sibel Uğur‐İşeri, Betül Baykan, Barış Salman, Garen Haryanyan, Emrah Yücesan, Yeşim Kesim, Çiğdem Özkara, Annapurna Poduri, Russell J. Buono, Thomas N. Ferraro, Michael R. Sperling, Warren Lo, Michael Privitera, Jacqueline A. French, Steven Schachter, Ruben I. Kuzniecky, Manu Hegde, Pouya Khankhanian, Katherine L. Helbig, Colin A. Ellis, (International League Against Epilepsy Consortium on Complex Epilepsies), (Epi25 Collaborative)

Epilepsia, Volume: 62, Issue: 7, Pages: 1518 - 1527

Swansea University Author: Robert Powell

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DOI (Published version): 10.1111/epi.16922

Abstract

ObjectiveParoxysmal 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 backgr...

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Published in: Epilepsia
ISSN: 0013-9580 1528-1167
Published: Wiley 2021
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa60623
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fullrecord <?xml version="1.0"?><rfc1807><datestamp>2022-08-15T10:24:21.1466828</datestamp><bib-version>v2</bib-version><id>60623</id><entry>2022-07-25</entry><title>Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations</title><swanseaauthors><author><sid>7c8ac48bb6ae4281930e4138f94a51b6</sid><firstname>Robert</firstname><surname>Powell</surname><name>Robert Powell</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2022-07-25</date><deptcode>FGMHL</deptcode><abstract>ObjectiveParoxysmal 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.MethodsConfounding 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.ResultsOur 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.SignificanceOur 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.</abstract><type>Journal Article</type><journal>Epilepsia</journal><volume>62</volume><journalNumber>7</journalNumber><paginationStart>1518</paginationStart><paginationEnd>1527</paginationEnd><publisher>Wiley</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>0013-9580</issnPrint><issnElectronic>1528-1167</issnElectronic><keywords>beta power, EEG, generalized epilepsy, GGE, oscillations, PRS</keywords><publishedDay>5</publishedDay><publishedMonth>7</publishedMonth><publishedYear>2021</publishedYear><publishedDate>2021-07-05</publishedDate><doi>10.1111/epi.16922</doi><url/><notes/><college>COLLEGE NANME</college><department>Medicine, Health and Life Science - Faculty</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>FGMHL</DepartmentCode><institution>Swansea University</institution><apcterm/><funders>Science Foundation Ireland. Grant Numbers: 16/RC/3948, 13/CDA/2223; European Regional Development Fund; FutureNeuro industry partners; Wellcome Trust. Grant Numbers: 084730, WT066056; Epilepsy Society, UK, NIHR. Grant Number: 08-08-SCC; GIHE. Grant Numbers: NIH R01-NS-49306-01, NIH R01-NS-053998; GSCFE. Grant Number: NIH R01-NS-064154-01; NIH. Grant Number: UL1TR001070; The Children&#x2019;s Hospital of Philadelphia; NHMRC. Grant Number: 1091593; The Royal Melbourne Hospital Foundation Lottery Grant; The RMH Neuroscience Foundation; European Union&#x2019;s Seventh Framework Programme (FP7/2007-2013). Grant Number: 279062; Department of Health&#x2019;s NIHR Biomedical Research Centers funding scheme, European Community. Grant Number: LSHM-CT2006-037315; German Research Foundation. Grant Number: SA434/4-1/4-26-1; European Science Foundation. Grant Numbers: 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. Grant Numbers: 01GS08120, 01GS08123; The Netherlands National Epilepsy Fund. Grant Number: 04-08; Research Grants Council of the Hong Kong Special Administrative Region. Grant Numbers: HKU7623/08 M, HKU7747/ 07 M, CUHK4466/06 M; Fonds National de la Recherche Scientifique; Fondation Erasme; Universit&#xE9; Libre de Bruxelles; NIHR Biomedical Research Centres Schem. Grant Number: P31753; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Grant Number: N01HD33348; German Ministry for Education and Research. Grant Number: 01EY1103; Helmholtz Zentrum M&#xFC;nchen &#x2013; German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria; Helmholtz Zentrum M&#xFC;nchen&#x2013;German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research and by the State of Bavaria; Munich Center of Health Sciences; Ludwig Maximilian University, as part of LMUinnovativ</funders><projectreference/><lastEdited>2022-08-15T10:24:21.1466828</lastEdited><Created>2022-07-25T11:20:05.2981776</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Medicine</level></path><authors><author><firstname>Remi</firstname><surname>Stevelink</surname><orcid>0000-0003-0214-7965</orcid><order>1</order></author><author><firstname>Jurjen J.</firstname><surname>Luykx</surname><order>2</order></author><author><firstname>Bochao D.</firstname><surname>Lin</surname><order>3</order></author><author><firstname>Costin</firstname><surname>Leu</surname><order>4</order></author><author><firstname>Dennis</firstname><surname>Lal</surname><order>5</order></author><author><firstname>Alexander W.</firstname><surname>Smith</surname><order>6</order></author><author><firstname>Dick</firstname><surname>Schijven</surname><order>7</order></author><author><firstname>Johannes A.</firstname><surname>Carpay</surname><order>8</order></author><author><firstname>Koen</firstname><surname>Rademaker</surname><order>9</order></author><author><firstname>Roiza A. Rodrigues</firstname><surname>Baldez</surname><order>10</order></author><author><firstname>Orrin</firstname><surname>Devinsky</surname><orcid>0000-0003-0044-4632</orcid><order>11</order></author><author><firstname>Kees P. J.</firstname><surname>Braun</surname><order>12</order></author><author><firstname>Floor E.</firstname><surname>Jansen</surname><order>13</order></author><author><firstname>Dirk J. A.</firstname><surname>Smit</surname><order>14</order></author><author><firstname>Bobby P. C.</firstname><surname>Koeleman</surname><order>15</order></author><author><firstname>Bassel</firstname><surname>Abou&#x2010;Khalil</surname><order>16</order></author><author><firstname>Pauls</firstname><surname>Auce</surname><order>17</order></author><author><firstname>Andreja</firstname><surname>Avbersek</surname><order>18</order></author><author><firstname>Melanie</firstname><surname>Bahlo</surname><order>19</order></author><author><firstname>David J.</firstname><surname>Balding</surname><order>20</order></author><author><firstname>Thomas</firstname><surname>Bast</surname><order>21</order></author><author><firstname>Larry</firstname><surname>Baum</surname><order>22</order></author><author><firstname>Albert J.</firstname><surname>Becker</surname><order>23</order></author><author><firstname>Felicitas</firstname><surname>Becker</surname><order>24</order></author><author><firstname>Bianca</firstname><surname>Berghuis</surname><order>25</order></author><author><firstname>Samuel F.</firstname><surname>Berkovic</surname><order>26</order></author><author><firstname>Katja E.</firstname><surname>Boysen</surname><order>27</order></author><author><firstname>Jonathan P.</firstname><surname>Bradfield</surname><order>28</order></author><author><firstname>Lawrence C.</firstname><surname>Brody</surname><order>29</order></author><author><firstname>Russell J.</firstname><surname>Buono</surname><order>30</order></author><author><firstname>Ellen</firstname><surname>Campbell</surname><order>31</order></author><author><firstname>Gregory D.</firstname><surname>Cascino</surname><order>32</order></author><author><firstname>Claudia B.</firstname><surname>Catarino</surname><order>33</order></author><author><firstname>Gianpiero L.</firstname><surname>Cavalleri</surname><order>34</order></author><author><firstname>Stacey S.</firstname><surname>Cherny</surname><order>35</order></author><author><firstname>Krishna</firstname><surname>Chinthapalli</surname><order>36</order></author><author><firstname>Alison J.</firstname><surname>Coffey</surname><order>37</order></author><author><firstname>Alastair</firstname><surname>Compston</surname><order>38</order></author><author><firstname>Antonietta</firstname><surname>Coppola</surname><order>39</order></author><author><firstname>Patrick</firstname><surname>Cossette</surname><order>40</order></author><author><firstname>John J.</firstname><surname>Craig</surname><order>41</order></author><author><firstname>Gerrit&#x2010;Jan</firstname><surname>Haan</surname><order>42</order></author><author><firstname>Peter De</firstname><surname>Jonghe</surname><order>43</order></author><author><firstname>Carolien G. 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spelling 2022-08-15T10:24:21.1466828 v2 60623 2022-07-25 Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations 7c8ac48bb6ae4281930e4138f94a51b6 Robert Powell Robert Powell true false 2022-07-25 FGMHL ObjectiveParoxysmal 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.MethodsConfounding 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.ResultsOur 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.SignificanceOur 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. Journal Article Epilepsia 62 7 1518 1527 Wiley 0013-9580 1528-1167 beta power, EEG, generalized epilepsy, GGE, oscillations, PRS 5 7 2021 2021-07-05 10.1111/epi.16922 COLLEGE NANME Medicine, Health and Life Science - Faculty COLLEGE CODE FGMHL Swansea University Science Foundation Ireland. Grant Numbers: 16/RC/3948, 13/CDA/2223; European Regional Development Fund; FutureNeuro industry partners; Wellcome Trust. Grant Numbers: 084730, WT066056; Epilepsy Society, UK, NIHR. Grant Number: 08-08-SCC; GIHE. Grant Numbers: NIH R01-NS-49306-01, NIH R01-NS-053998; GSCFE. Grant Number: NIH R01-NS-064154-01; NIH. Grant Number: UL1TR001070; The Children’s Hospital of Philadelphia; NHMRC. Grant Number: 1091593; The Royal Melbourne Hospital Foundation Lottery Grant; The RMH Neuroscience Foundation; European Union’s Seventh Framework Programme (FP7/2007-2013). Grant Number: 279062; Department of Health’s NIHR Biomedical Research Centers funding scheme, European Community. Grant Number: LSHM-CT2006-037315; German Research Foundation. Grant Number: SA434/4-1/4-26-1; European Science Foundation. Grant Numbers: 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. Grant Numbers: 01GS08120, 01GS08123; The Netherlands National Epilepsy Fund. Grant Number: 04-08; Research Grants Council of the Hong Kong Special Administrative Region. Grant Numbers: HKU7623/08 M, HKU7747/ 07 M, CUHK4466/06 M; Fonds National de la Recherche Scientifique; Fondation Erasme; Université Libre de Bruxelles; NIHR Biomedical Research Centres Schem. Grant Number: P31753; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Grant Number: N01HD33348; German Ministry for Education and Research. Grant Number: 01EY1103; Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria; Helmholtz Zentrum München–German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research and by the State of Bavaria; Munich Center of Health Sciences; Ludwig Maximilian University, as part of LMUinnovativ 2022-08-15T10:24:21.1466828 2022-07-25T11:20:05.2981776 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Remi Stevelink 0000-0003-0214-7965 1 Jurjen J. Luykx 2 Bochao D. Lin 3 Costin Leu 4 Dennis Lal 5 Alexander W. Smith 6 Dick Schijven 7 Johannes A. Carpay 8 Koen Rademaker 9 Roiza A. Rodrigues Baldez 10 Orrin Devinsky 0000-0003-0044-4632 11 Kees P. J. Braun 12 Floor E. Jansen 13 Dirk J. A. Smit 14 Bobby P. C. Koeleman 15 Bassel Abou‐Khalil 16 Pauls Auce 17 Andreja Avbersek 18 Melanie Bahlo 19 David J. Balding 20 Thomas Bast 21 Larry Baum 22 Albert J. Becker 23 Felicitas Becker 24 Bianca Berghuis 25 Samuel F. Berkovic 26 Katja E. Boysen 27 Jonathan P. Bradfield 28 Lawrence C. Brody 29 Russell J. Buono 30 Ellen Campbell 31 Gregory D. Cascino 32 Claudia B. Catarino 33 Gianpiero L. Cavalleri 34 Stacey S. Cherny 35 Krishna Chinthapalli 36 Alison J. Coffey 37 Alastair Compston 38 Antonietta Coppola 39 Patrick Cossette 40 John J. Craig 41 Gerrit‐Jan Haan 42 Peter De Jonghe 43 Carolien G. F. Kovel 44 Norman Delanty 45 Chantal Depondt 46 Dennis J. Dlugos 47 Colin P. Doherty 48 Christian E. Elger 49 Johan G. Eriksson 50 Thomas N. Ferraro 51 Martha Feucht 52 Ben Francis 53 Andre Franke 54 Jacqueline A. French 55 Saskia Freytag 56 Verena Gaus 57 Eric B. Geller 58 Christian Gieger 59 Tracy Glauser 60 Simon Glynn 61 David B. Goldstein 62 Hongsheng Gui 63 Youling Guo 64 Kevin F. Haas 65 Hakon Hakonarson 66 Kerstin Hallmann 67 Sheryl Haut 68 Erin L. Heinzen 69 Ingo Helbig 70 Christian Hengsbach 71 Helle Hjalgrim 72 Michele Iacomino 73 Andrés Ingason 74 Jennifer Jamnadas‐Khoda 75 Michael R. Johnson 76 Reetta Kälviäinen 77 Anne‐Mari Kantanen 78 Dalia Kasperavičiūte 79 Dorothee Kasteleijn‐Nolst Trenite 80 Heidi E. Kirsch 81 Robert C. Knowlton 82 Roland Krause 83 Martin Krenn 84 Wolfram S. Kunz 85 Ruben Kuzniecky 86 Patrick Kwan 87 Yu‐Lung Lau 88 Anna‐Elina Lehesjoki 89 Holger Lerche 90 Wolfgang Lieb 91 Dick Lindhout 92 Warren D. Lo 93 Iscia Lopes‐Cendes 94 Daniel H. Lowenstein 95 Alberto Malovini 96 Anthony G. Marson 97 Thomas Mayer 98 Mark McCormack 99 James L. Mills 100 Nasir Mirza 101 Martina Moerzinger 102 Rikke S. Møller 103 Anne M. Molloy 104 Hiltrud Muhle 105 Mark Newton 106 Ping‐Wing Ng 107 Markus M. Nöthen 108 Peter Nürnberg 109 Terence J. O’Brien 110 Karen L. Oliver 111 Aarno Palotie 112 Faith Pangilinan 113 Sarah Peter 114 Slavé Petrovski 115 Annapurna Poduri 116 Michael Privitera 117 Rodney Radtke 118 Sarah Rau 119 Philipp S. Reif 120 Eva M. Reinthaler 121 Felix Rosenow 122 Josemir W. Sander 123 Thomas Sander 124 Theresa Scattergood 125 Steven C. Schachter 126 Christoph J. Schankin 127 Ingrid E. Scheffer 128 Bettina Schmitz 129 Susanne Schoch 130 Pak C. Sham 131 Jerry J. Shih 132 Graeme J. Sills 133 Sanjay M. Sisodiya 134 Lisa Slattery 135 David F. Smith 136 Michael C. Smith 137 Philip E. Smith 138 Anja C. M. Sonsma 139 Doug Speed 140 Michael R. Sperling 141 Bernhard J. Steinhoff 142 Ulrich Stephani 143 Konstantin Strauch 144 Pasquale Striano 145 Hans Stroink 146 Rainer Surges 147 K. Meng Tan 148 Liu Lin Thio 149 G. Neil Thomas 150 Marian Todaro 151 Rossana Tozzi 152 Maria S. Vari 153 Eileen P. G. Vining 154 Frank Visscher 155 Sarah Spiczak 156 Nicole M. Walley 157 Yvonne G. Weber 158 Zhi Wei 159 Ruta Mameniskiene 160 Judith Weisenberg 161 Christopher D. Whelan 162 Peter Widdess‐Walsh 163 Markus Wolff 164 Stefan Wolking 165 Wanling Yang 166 Federico Zara 167 Fritz Zimprich 168 Yen‐Chen Anne Feng 169 Daniel P. Howrigan 170 Liam E. Abbott 171 Katherine Tashman 172 Felecia Cerrato 173 Dennis Lal 174 Claire Churchhouse 175 Namrata Gupta 176 Stacey B. Gabriel 177 Mark J. Daly 178 Eric S. Lander 179 Benjamin M. Neale 180 Samuel F. Berkovic 181 Holger Lerche 182 David B. Goldstein 183 Daniel H. Lowenstein 184 Gianpiero L. Cavalleri 185 Patrick Cossette 186 Chris Cotsapas 187 Peter De Jonghe 188 Tracy Dixon‐Salazar 189 Renzo Guerrini 190 Hakon Hakonarson 191 Erin L. Heinzen 192 Ingo Helbig 193 Patrick Kwan 194 Slavé Petrovski 195 Sitharthan Kamalakaran 196 Sanjay M. Sisodiya 197 Randy Stewart 198 Sarah Weckhuysen 199 Dennis J. Dlugos 200 Ingrid E. Scheffer 201 Pasquale Striano 202 Catharine Freyer 203 Roland Krause 204 Patrick May 205 Kevin McKenna 206 Brigid M. Regan 207 Susannah T. Bellows 208 Caitlin A. Bennett 209 Esther M.C. Johns 210 Alexandra Macdonald 211 Hannah Shilling 212 Rosemary Burgess 213 Dorien Weckhuysen 214 Melanie Bahlo 215 Terence J. O'Brien 216 Marian Todaro 217 Hannah Stamberger 218 Chantal Depondt 219 Danielle M. Andrade 220 Tara R. Sadoway 221 Kelly Mo 222 Heinz Krestel 223 Sabina Gallati 224 Savvas S. Papacostas 225 Ioanna Kousiappa 226 George A. Tanteles 227 Katalin Štěrbová 228 Markéta Vlčková 229 Lucie Sedláčková 230 Petra Laššuthová 231 Karl Martin Klein 232 Felix Rosenow 233 Philipp S. Reif 234 Susanne Knake 235 Wolfram S. Kunz 236 Gábor Zsurka 237 Christian E. Elger 238 Jürgen Bauer 239 Michael Rademacher 240 Manuela Pendziwiat 241 Hiltrud Muhle 242 Annika Rademacher 243 Andreas Baalen 244 Sarah Spiczak 245 Ulrich Stephani 246 Zaid Afawi 247 Amos D. Korczyn 248 Moien Kanaan 249 Christina Canavati 250 Gerhard Kurlemann 251 Karen Müller‐Schlüter 252 Gerhard Kluger 253 Martin Häusler 254 Ilan Blatt 255 Johannes R. Lemke 256 Ilona Krey 257 Yvonne G. Weber 258 Stefan Wolking 259 Felicitas Becker 260 Christian Hengsbach 261 Sarah Rau 262 Ana F. Maisch 263 Bernhard J. Steinhoff 264 Andreas Schulze‐Bonhage 265 Susanne Schubert‐Bast 266 Herbert Schreiber 267 Ingo Borggräfe 268 Christoph J. Schankin 269 Thomas Mayer 270 Rudolf Korinthenberg 271 Knut Brockmann 272 Dieter Dennig 273 Rene Madeleyn 274 Reetta Kälviäinen 275 Pia Auvinen 276 Anni Saarela 277 Tarja Linnankivi 278 Anna‐Elina Lehesjoki 279 Mark I. Rees 280 Seo‐Kyung Chung 281 William O. Pickrell 282 Robert Powell 283 Natascha Schneider 284 Simona Balestrini 285 Sara Zagaglia 286 Vera Braatz 287 Anthony G. Marson 288 Michael R. Johnson 289 Pauls Auce 290 Graeme J. Sills 291 Larry W. Baum 292 Pak C. Sham 293 Stacey S. Cherny 294 Colin H.T. Lui 295 Nina Barišić 296 Norman Delanty 297 Colin P. Doherty 298 Arif Shukralla 299 Mark McCormack 300 Hany El‐Naggar 301 Laura Canafoglia 302 Silvana Franceschetti 303 Barbara Castellotti 304 Tiziana Granata 305 Federico Zara 306 Michele Iacomino 307 Francesca Madia 308 Maria Stella Vari 309 Maria Margherita Mancardi 310 Vincenzo Salpietro 311 Francesca Bisulli 312 Paolo Tinuper 313 Laura Licchetta 314 Tommaso Pippucci 315 Carlotta Stipa 316 Raffaella Minardi 317 Antonio Gambardella 318 Angelo Labate 319 Grazia Annesi 320 Lorella Manna 321 Monica Gagliardi 322 Elena Parrini 323 Davide Mei 324 Annalisa Vetro 325 Claudia Bianchini 326 Martino Montomoli 327 Viola Doccini 328 Carla Marini 329 Toshimitsu Suzuki 330 Yushi Inoue 331 Kazuhiro Yamakawa 332 Birute Tumiene 333 Lynette G. Sadleir 334 Chontelle King 335 Emily Mountier 336 S. Hande Caglayan 337 Mutluay Arslan 338 Zuhal Yapıcı 339 Uluc Yis 340 Pınar Topaloglu 341 Bulent Kara 342 Dilsad Turkdogan 343 Aslı Gundogdu‐Eken 344 Nerses Bebek 345 Sibel Uğur‐İşeri 346 Betül Baykan 347 Barış Salman 348 Garen Haryanyan 349 Emrah Yücesan 350 Yeşim Kesim 351 Çiğdem Özkara 352 Annapurna Poduri 353 Russell J. Buono 354 Thomas N. Ferraro 355 Michael R. Sperling 356 Warren Lo 357 Michael Privitera 358 Jacqueline A. French 359 Steven Schachter 360 Ruben I. Kuzniecky 361 Manu Hegde 362 Pouya Khankhanian 363 Katherine L. Helbig 364 Colin A. Ellis 365 (International League Against Epilepsy Consortium on Complex Epilepsies) 366 (Epi25 Collaborative) 367 60623__24913__d11a7f014407419d831dae97647f7ec5.pdf 60623.pdf 2022-08-15T10:22:24.4465670 Output 815290 application/pdf Version of Record true © 2021 The Authors. This is an open access article under the terms of the Creative Commons Attribution License true eng http://creativecommons.org/licenses/by/4.0/
title Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations
spellingShingle Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations
Robert Powell
title_short 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_sort Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations
author_id_str_mv 7c8ac48bb6ae4281930e4138f94a51b6
author_id_fullname_str_mv 7c8ac48bb6ae4281930e4138f94a51b6_***_Robert Powell
author Robert Powell
author2 Remi Stevelink
Jurjen J. Luykx
Bochao D. Lin
Costin Leu
Dennis Lal
Alexander W. Smith
Dick Schijven
Johannes A. Carpay
Koen Rademaker
Roiza A. Rodrigues Baldez
Orrin Devinsky
Kees P. J. Braun
Floor E. Jansen
Dirk J. A. Smit
Bobby P. C. Koeleman
Bassel Abou‐Khalil
Pauls Auce
Andreja Avbersek
Melanie Bahlo
David J. Balding
Thomas Bast
Larry Baum
Albert J. Becker
Felicitas Becker
Bianca Berghuis
Samuel F. Berkovic
Katja E. Boysen
Jonathan P. Bradfield
Lawrence C. Brody
Russell J. Buono
Ellen Campbell
Gregory D. Cascino
Claudia B. Catarino
Gianpiero L. Cavalleri
Stacey S. Cherny
Krishna Chinthapalli
Alison J. Coffey
Alastair Compston
Antonietta Coppola
Patrick Cossette
John J. Craig
Gerrit‐Jan Haan
Peter De Jonghe
Carolien G. F. Kovel
Norman Delanty
Chantal Depondt
Dennis J. Dlugos
Colin P. Doherty
Christian E. Elger
Johan G. Eriksson
Thomas N. Ferraro
Martha Feucht
Ben Francis
Andre Franke
Jacqueline A. French
Saskia Freytag
Verena Gaus
Eric B. Geller
Christian Gieger
Tracy Glauser
Simon Glynn
David B. Goldstein
Hongsheng Gui
Youling Guo
Kevin F. Haas
Hakon Hakonarson
Kerstin Hallmann
Sheryl Haut
Erin L. Heinzen
Ingo Helbig
Christian Hengsbach
Helle Hjalgrim
Michele Iacomino
Andrés Ingason
Jennifer Jamnadas‐Khoda
Michael R. Johnson
Reetta Kälviäinen
Anne‐Mari Kantanen
Dalia Kasperavičiūte
Dorothee Kasteleijn‐Nolst Trenite
Heidi E. Kirsch
Robert C. Knowlton
Roland Krause
Martin Krenn
Wolfram S. Kunz
Ruben Kuzniecky
Patrick Kwan
Yu‐Lung Lau
Anna‐Elina Lehesjoki
Holger Lerche
Wolfgang Lieb
Dick Lindhout
Warren D. Lo
Iscia Lopes‐Cendes
Daniel H. Lowenstein
Alberto Malovini
Anthony G. Marson
Thomas Mayer
Mark McCormack
James L. Mills
Nasir Mirza
Martina Moerzinger
Rikke S. Møller
Anne M. Molloy
Hiltrud Muhle
Mark Newton
Ping‐Wing Ng
Markus M. Nöthen
Peter Nürnberg
Terence J. O’Brien
Karen L. Oliver
Aarno Palotie
Faith Pangilinan
Sarah Peter
Slavé Petrovski
Annapurna Poduri
Michael Privitera
Rodney Radtke
Sarah Rau
Philipp S. Reif
Eva M. Reinthaler
Felix Rosenow
Josemir W. Sander
Thomas Sander
Theresa Scattergood
Steven C. Schachter
Christoph J. Schankin
Ingrid E. Scheffer
Bettina Schmitz
Susanne Schoch
Pak C. Sham
Jerry J. Shih
Graeme J. Sills
Sanjay M. Sisodiya
Lisa Slattery
David F. Smith
Michael C. Smith
Philip E. Smith
Anja C. M. Sonsma
Doug Speed
Michael R. Sperling
Bernhard J. Steinhoff
Ulrich Stephani
Konstantin Strauch
Pasquale Striano
Hans Stroink
Rainer Surges
K. Meng Tan
Liu Lin Thio
G. Neil Thomas
Marian Todaro
Rossana Tozzi
Maria S. Vari
Eileen P. G. Vining
Frank Visscher
Sarah Spiczak
Nicole M. Walley
Yvonne G. Weber
Zhi Wei
Ruta Mameniskiene
Judith Weisenberg
Christopher D. Whelan
Peter Widdess‐Walsh
Markus Wolff
Stefan Wolking
Wanling Yang
Federico Zara
Fritz Zimprich
Yen‐Chen Anne Feng
Daniel P. Howrigan
Liam E. Abbott
Katherine Tashman
Felecia Cerrato
Dennis Lal
Claire Churchhouse
Namrata Gupta
Stacey B. Gabriel
Mark J. Daly
Eric S. Lander
Benjamin M. Neale
Samuel F. Berkovic
Holger Lerche
David B. Goldstein
Daniel H. Lowenstein
Gianpiero L. Cavalleri
Patrick Cossette
Chris Cotsapas
Peter De Jonghe
Tracy Dixon‐Salazar
Renzo Guerrini
Hakon Hakonarson
Erin L. Heinzen
Ingo Helbig
Patrick Kwan
Slavé Petrovski
Sitharthan Kamalakaran
Sanjay M. Sisodiya
Randy Stewart
Sarah Weckhuysen
Dennis J. Dlugos
Ingrid E. Scheffer
Pasquale Striano
Catharine Freyer
Roland Krause
Patrick May
Kevin McKenna
Brigid M. Regan
Susannah T. Bellows
Caitlin A. Bennett
Esther M.C. Johns
Alexandra Macdonald
Hannah Shilling
Rosemary Burgess
Dorien Weckhuysen
Melanie Bahlo
Terence J. O'Brien
Marian Todaro
Hannah Stamberger
Chantal Depondt
Danielle M. Andrade
Tara R. Sadoway
Kelly Mo
Heinz Krestel
Sabina Gallati
Savvas S. Papacostas
Ioanna Kousiappa
George A. Tanteles
Katalin Štěrbová
Markéta Vlčková
Lucie Sedláčková
Petra Laššuthová
Karl Martin Klein
Felix Rosenow
Philipp S. Reif
Susanne Knake
Wolfram S. Kunz
Gábor Zsurka
Christian E. Elger
Jürgen Bauer
Michael Rademacher
Manuela Pendziwiat
Hiltrud Muhle
Annika Rademacher
Andreas Baalen
Sarah Spiczak
Ulrich Stephani
Zaid Afawi
Amos D. Korczyn
Moien Kanaan
Christina Canavati
Gerhard Kurlemann
Karen Müller‐Schlüter
Gerhard Kluger
Martin Häusler
Ilan Blatt
Johannes R. Lemke
Ilona Krey
Yvonne G. Weber
Stefan Wolking
Felicitas Becker
Christian Hengsbach
Sarah Rau
Ana F. Maisch
Bernhard J. Steinhoff
Andreas Schulze‐Bonhage
Susanne Schubert‐Bast
Herbert Schreiber
Ingo Borggräfe
Christoph J. Schankin
Thomas Mayer
Rudolf Korinthenberg
Knut Brockmann
Dieter Dennig
Rene Madeleyn
Reetta Kälviäinen
Pia Auvinen
Anni Saarela
Tarja Linnankivi
Anna‐Elina Lehesjoki
Mark I. Rees
Seo‐Kyung Chung
William O. Pickrell
Robert Powell
Natascha Schneider
Simona Balestrini
Sara Zagaglia
Vera Braatz
Anthony G. Marson
Michael R. Johnson
Pauls Auce
Graeme J. Sills
Larry W. Baum
Pak C. Sham
Stacey S. Cherny
Colin H.T. Lui
Nina Barišić
Norman Delanty
Colin P. Doherty
Arif Shukralla
Mark McCormack
Hany El‐Naggar
Laura Canafoglia
Silvana Franceschetti
Barbara Castellotti
Tiziana Granata
Federico Zara
Michele Iacomino
Francesca Madia
Maria Stella Vari
Maria Margherita Mancardi
Vincenzo Salpietro
Francesca Bisulli
Paolo Tinuper
Laura Licchetta
Tommaso Pippucci
Carlotta Stipa
Raffaella Minardi
Antonio Gambardella
Angelo Labate
Grazia Annesi
Lorella Manna
Monica Gagliardi
Elena Parrini
Davide Mei
Annalisa Vetro
Claudia Bianchini
Martino Montomoli
Viola Doccini
Carla Marini
Toshimitsu Suzuki
Yushi Inoue
Kazuhiro Yamakawa
Birute Tumiene
Lynette G. Sadleir
Chontelle King
Emily Mountier
S. Hande Caglayan
Mutluay Arslan
Zuhal Yapıcı
Uluc Yis
Pınar Topaloglu
Bulent Kara
Dilsad Turkdogan
Aslı Gundogdu‐Eken
Nerses Bebek
Sibel Uğur‐İşeri
Betül Baykan
Barış Salman
Garen Haryanyan
Emrah Yücesan
Yeşim Kesim
Çiğdem Özkara
Annapurna Poduri
Russell J. Buono
Thomas N. Ferraro
Michael R. Sperling
Warren Lo
Michael Privitera
Jacqueline A. French
Steven Schachter
Ruben I. Kuzniecky
Manu Hegde
Pouya Khankhanian
Katherine L. Helbig
Colin A. Ellis
(International League Against Epilepsy Consortium on Complex Epilepsies)
(Epi25 Collaborative)
format Journal article
container_title Epilepsia
container_volume 62
container_issue 7
container_start_page 1518
publishDate 2021
institution Swansea University
issn 0013-9580
1528-1167
doi_str_mv 10.1111/epi.16922
publisher Wiley
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description ObjectiveParoxysmal 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.MethodsConfounding 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.ResultsOur 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.SignificanceOur 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.
published_date 2021-07-05T04:18:53Z
_version_ 1763754255014952960
score 11.028886

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