Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USASiwei Chen, Felecia Cerrato, Claire Churchhouse, Caroline Cusick, Mark J. Daly, Yen-Chen Anne Feng, Daniel P. Howrigan, Calwing Liao, Steven M. McCarroll, Aarno Palotie & Benjamin M. NealeProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USASiwei Chen, Harrison Brand, Claire Churchhouse, Mark J. Daly, Yen-Chen Anne Feng, Jack M. Fu, Stacey Gabriel, Riley Grant, Namrata Gupta, Henrike Heyne, Daniel P. Howrigan, Calwing Liao, Chelsea Lowther, Steven M. McCarroll, Matthew Solomonson, Michael E. Talkowski, Nick Watts, Isaac Wong & Benjamin M. NealeAnalytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USASiwei Chen, Claire Churchhouse, Mark J. Daly, Daniel P. Howrigan, Calwing Liao, Aarno Palotie & Benjamin M. NealeDepartment of Neurology, Vanderbilt University Medical Center, Nashville, TN, USABassel W. Abou-Khalil, Kevin Haas & Randip S. TanejaTel-Aviv University Sackler Faculty of Medicine, Ramat Aviv, IsraelZaid Afawi, Ilan Blatt & Amos D. KorczynUniversity Health Network, University of Toronto, Toronto, ON, CanadaQuratulain Zulfiqar Ali, Danielle M. Andrade, Karen Barboza & Paula MarquesIRCCS Istituto Giannina Gaslini, Genoa, ItalyElisabetta Amadori, Michele Iacomino, Francesca Madia, Antonella Riva, Vincenzo Salpietro, Marcello Scala, Paolo Scudieri, Pasquale Striano, Maria Stella Vari & Federico ZaraDepartment of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, AustraliaAlison Anderson, Patrick Kwan, Terence J. O’Brien, Slavé Petrovski & Marian TodaroDepartment of Neuroscience, The School of Translational Medicine, Alfred Health, Monash University, Melbourne, Victoria, AustraliaAlison Anderson, Patrick Kwan, Terence J. O’Brien & Marian TodaroNeurology Department, Aneurin Bevan University Health Board, Newport, UKJoe Anderson & Charlotte LawthomDepartment of Medical and Surgical Sciences, Neuroscience Research Center, Magna Graecia University, Catanzaro, ItalyGrazia Annesi, Monica Gagliardi, Ilaria Sammarra & Mariagrazia TalaricoDepartment of Child Neurology, Gülhane Education and Research Hospital, Health Sciences University, Ankara, TurkeyMutluay ArslanSt George’s University Hospital NHS Foundation Trust, London, UKPauls AucePopulation Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, AustraliaMelanie BahloDepartment of Biology, University of Melbourne, Parkville, Victoria, AustraliaMelanie BahloSwansea University Medical School, Swansea University, Swansea, UKMark D. Baker, Seo-Kyung Chung, Beata Fonferko-Shadrach, Charlotte Lawthom, William O. Pickrell, Robert H. W. Powell & Mark I. ReesDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, ItalyGanna Balagura, Antonella Riva, Marcello Scala, Paolo Scudieri, Pasquale Striano & Federico ZaraDepartment of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UKSimona Balestrini, Vera Braatz, Costin Leu, Natascha Schneider, Sanjay M. Sisodiya & Sara ZagagliaChalfont Centre for Epilepsy, Chalfont-St-Peter, UKSimona Balestrini, Vera Braatz, Natascha Schneider, Sanjay M. Sisodiya & Sara ZagagliaData Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USAEric Banks, Laura Gauthier & Sam NovodNeuroscience Department, Meyer Children’s Hospital IRCCS, Florence, ItalyCarmen Barba, Claudia Bianchini, Viola Doccini, Renzo Guerrini, Davide Mei, Martino Montomoli, Elena Parrini & Annalisa VetroClinical Neurophysiology and Epileptology Department, Timone Hospital, Marseille, FranceFabrice BartolomeiDivision of Psychiatry, University College London, London, UKNick Bass & Andrew McQuillanDepartment of Psychiatry, The University of Hong Kong, Pokulam, Hong Kong, ChinaLarry W. Baum & Pak C. ShamDepartment of Epileptology, University of Bonn Medical Centre, Bonn, GermanyTobias H. Baumgartner, Wolfram S. Kunz, Rainer Surges, Randi von Wrede & Gábor ZsurkaDepartment of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, TurkeyBetül Baykan, Garen Haryanyan & Yeşim KesimDepartment of Child Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, TurkeyNerses Bebek, Pınar Topaloglu & Zuhal YapıcıDepartment of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, TurkeyNerses Bebek, Barış Salman & Sibel Uğur-İşeriDepartment of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, GermanyFelicitas Becker, Christian Bosselmann, Christian Hengsbach, Josua Kegele, Stephan Lauxmann, Holger Lerche, Sarah Rau, Yvonne G. Weber & Stefan WolkingDepartment of Neurology, University of Ulm, Ulm, GermanyFelicitas BeckerEpilepsy Research Centre, University of Melbourne, Austin Health, Heidelberg, Victoria, AustraliaCaitlin A. Bennett, Olivia Hoeper, Stephanie L. Leech, Brigid M. Regan, Ingrid E. Scheffer & Samuel F. BerkovicDepartment of Neurology, American University of Beirut Medical Center, Beirut, LebanonAhmad Beydoun & Wassim NasreddineDepartment of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, ItalyFrancesca Bisulli, Lorenzo Ferri, Lorenzo Muccioli, Federica Pondrelli & Paolo TinuperIRCCS Istituto delle Scienze Neurologiche di Bologna, (Reference Center for Rare and Complex Epilepsies – EpiCARE), Bologna, ItalyFrancesca Bisulli, Lidia Di Vito, Lorenzo Ferri, Laura Licchetta, Raffaella Minardi, Barbara Mostacci, Carlotta Stipa & Paolo TinuperDivision of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UKDouglas Blackwood, Mandy Johnstone & Andrew McIntoshDepartment of Neurology, Sheba Medical Center, Ramat Gan, IsraelIlan BlattDepartment of Pediatric Neurology, Dr von Hauner Children’s Hospital, Ludwig Maximilians University, Munich, GermanyIngo BorggräfeCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USAHarrison Brand, Jack M. Fu, Calwing Liao, Chelsea Lowther, Michael E. Talkowski & Isaac WongDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USAHarrison Brand, Jack M. Fu, Chelsea Lowther & Michael E. TalkowskiChildren’s Hospital, Dept. of Pediatric Neurology, University Medical Center Göttingen, Göttingen, GermanyKnut BrockmannDivision of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, USARussell J. Buono, Mahgenn Cosico, Dennis J. Dlugos, Mark Fitzgerald, Ethan Goldberg, Hakon Hakonarson, Ingo Helbig, Naomi Lewin, David Lewis-Smith & Priya VaidiswaranDepartment of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USARussell J. Buono & Thomas N. FerraroDepartment of Neurology, Thomas Jefferson University Hospital, Philadelphia, PA, USARussell J. BuonoGenomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USARobyn M. Busch, Dennis Lal & Costin LeuCleveland Clinic Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USARobyn M. Busch, Lisa Ferguson, Lara Jehi, Jean Khoury, Dennis Lal & Imad M. NajmDepartment of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH, USARobyn M. Busch, Lara Jehi, Jean Khoury & Imad M. NajmDepartment of Molecular Biology and Genetics, Bogaziçi University, Istanbul, TurkeyS. Hande Caglayan & Aslı Gundogdu-EkenIntegrated Diagnostics for Epilepsy, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, ItalyLaura CanafogliaHereditary Research Lab, Bethlehem University, Bethlehem, PalestineChristina Canavati & Moien KanaanUnit of Medical Genetics and Neurogenetics, Department of Diagnostic and Technology, Fondazione IRCCS Istituto Neurologico Carlo Besta Milano, Milan, ItalyBarbara CastellottiSchool of Pharmacy and Biomolecular Sciences, The Royal College of Surgeons in Ireland, Dublin, IrelandGianpiero L. Cavalleri, Norman Delanty, Austin Lacey & Peter Widdess-WalshThe FutureNeuro Research Centre, Dublin, IrelandGianpiero L. Cavalleri, Norman Delanty, Colin P. Doherty, Hany El-Naggar, Austin Lacey & Peter Widdess-WalshEpilepsy Unit, Department of Neurosurgery, Centre Hospitalier Sainte-Anne, and University Paris Descartes, Paris, FranceFrancine ChassouxDepartment of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, CanadaChristina Cherian, Karl Martin Klein, Andrea Salmon & Samuel WiebeDepartment of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelStacey S. ChernyDepartment of Pharmacology and Pharmacy, The University of Hong Kong, Pokfulam, Hong Kong, ChinaChing-Lung CheungDepartment of Pediatric Neurology, Chang Gung Memorial Hospital, Taoyuan, TaiwanI-Jun Chou, Po-Chen Hung & Kuang-Lin LinKids Research, Children’s Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, AustraliaSeo-Kyung ChungBrain & Mind Centre, Faculty of Medicine & Health, University of Sydney, Sydney, New South Wales, AustraliaSeo-Kyung Chung & Mark I. ReesNeuropsychiatry Laboratory, IRCCS Santa Lucia Foundation, Rome, ItalyValentina Ciullo, Tommaso Gili, Fabrizio Piras, Federica Piras & Gianfranco SpallettaDepartment of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, ItalyValentina CiulloCincinnati Children’s Hospital Medical Center, Cincinnati, OH, USAPeggy O. Clark & Tracy A. GlauserNeurology, Massachusetts General Hospital, Boston, MA, USAAndrew J. Cole, Christopher M. McGraw & Aarno PalotieThe Epilepsy NeuroGenetics Initiative (ENGIN), Children’s Hospital of Philadelphia, Philadelphia, PA, USAMahgenn Cosico, Mark Fitzgerald, Ethan Goldberg, Ingo Helbig, Naomi Lewin & Priya VaidiswaranDepartment of Neurosciences, Université de Montréal, Montréal, CA, CanadaPatrick CossetteYale School of Medicine, New Haven, CT, USAChris Cotsapas & Heinz KrestelInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, FinlandMark J. DalyDivision of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USALea K. Davis & Donald HucksDepartment of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USALea K. DavisDepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USALea K. DavisVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USALea K. Davis & Donald HucksApplied & Translational Neurogenomics Group, VIB Center for Molecular Neurology, VIB, Antwerp, BelgiumPeter De Jonghe, Hannah Stamberger & Sarah WeckhuysenDepartment of Neurology, Antwerp University Hospital, Edegem, BelgiumPeter De Jonghe, Hannah Stamberger & Sarah WeckhuysenTranslational Neurosciences, Faculty of Medicine and Health Science, University of Antwerp, Antwerp, BelgiumPeter De Jonghe, Hannah Stamberger & Sarah WeckhuysenDepartment of Neurology, Beaumont Hospital, Dublin, IrelandNorman Delanty, Hany El-Naggar & Peter Widdess-WalshPrivate Neurological Practice, Stuttgart, GermanyDieter DennigDepartment of Neurology, CUB Erasme Hospital, Hôpital Universitaire de Bruxelles (H.U.B.), Université Libre de Bruxelles (ULB), Brussels, BelgiumChantal DepondtDepartment of Clinical Neurophysiology, Lille University Medical Center, EA, University of Lille, Lille, FrancePhilippe DerambureDepartment of Neurology, New York University/Langone Health, New York, NY, USAOrrin Devinsky & Jacqueline A. FrenchSheppard Pratt, Baltimore, MD, USAFaith DickersonPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USADennis J. DlugosNeurology Department, St. James’s Hospital, Dublin, IrelandColin P. DohertyDepartment of Neurology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USAColin A. Ellis, Mark Fitzgerald & Ingo HelbigDivision of Neurology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USALeon Epstein, Enrique Rojas & Kathryn R. SparksDepartment of Paediatrics and Child Health, University of Otago, Wellington, New ZealandMeghan Evans, Chontelle King & Lynette G. SadleirHuman Genetics Training Program, Vanderbilt University, Nashville, TN, USAAnnika Faucon & David WuPsychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USAYen-Chen Anne Feng & Aarno PalotieAnalytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USAYen-Chen Anne Feng, Matthew Solomonson & Nick WattsDivision of Biostatistics, Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, TaiwanYen-Chen Anne FengDepartment of Pharmacology and Psychiatry, University of Pennsylvania Perlman School of Medicine, Philadelphia, PA, USAThomas N. FerraroLuxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, LuxembourgIzabela Ferreira Da Silva, Roland Krause, Patrick May & Milena ZizovicDepartment of Pediatrics and Neonatology, Medical University of Vienna, Vienna, AustriaMartha FeuchtDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USAMadeline C. Fields, Maite La Vega-Talbott, Lara Marcuse, Patricia McGoldrick, Hillary R. Raynes & Steven M. WolfInstitute of Neurology, Department of Medical and Surgical Sciences, University “Magna Graecia”, Catanzaro, ItalyFrancesco Fortunato & Antonio GambardellaNeurophysiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, ItalySilvana FranceschettiDepartment of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, ItalyElena Freri, Tiziana Granata & Francesca RagonaIRCCS Azienda Ospedaliero-Universitaria di Bologna, Medical Genetics Unit, Bologna, ItalyTania Giangregorio & Tommaso PippucciIMT School for Advanced Studies Lucca, Lucca, ItalyTommaso GiliDepartment of Neurology, Baylor College of Medicine, Houston, TX, USAAlica Goldman & Jeffrey L. NoebelsInstitute for Genomic Medicine, Columbia University Medical Center, New York, NY, USADavid B. GoldsteinDepartment of Pediatrics, Nationwide Children’s Hospital, Columbia, OH, USADavid A. Greenberg & William C. StewartDepartment of NEUROFARBA, University of Florence, Florence, ItalyRenzo Guerrini & Elena ParriniDivision of Neuropediatrics and Social Pediatrics, Department of Pediatrics, University Hospital, RWTH Aachen, Aachen, GermanyMartin HäuslerDepartment of Neurology, University of California, San Francisco, CA, USAManu Hegde & Daniel H. LowensteinDivision of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAErin L. HeinzenDepartment of Neuropediatrics, University Medical Center Schleswig-Holstein, Christian-Albrechts-University, Kiel, GermanyIngo Helbig, Hiltrud Muhle, Manuela Pendziwiat, Annika Rademacher, Ulrich Stephani, Andreas van Baalen & Sarah von SpiczakInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, GermanyIngo Helbig & Manuela PendziwiatDepartment of Biomedical and Health Informatics (DBHi), Children’s Hospital of Philadelphia, Philadelphia, PA, USAIngo Helbig & David Lewis-SmithHasso Plattner Institute, Digital Engineering Faculty, University of Potsdam, Potsdam, GermanyHenrike HeyneGeneral Medical Research Center, School of Medicine, Fukuoka University, Fukuoka, JapanShinichi HiroseDepartment of Neurology, University Hospital of Strasbourg, Strasbourg, FranceEdouard HirschDepartment of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, TaiwanChen-Jui Ho, Chih-Hsiang Lin & Meng-Han TsaiNational Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorder, Shizuoka, JapanYushi InoueEpilepsy Clinic, Hospital Sirio-Libanes, Sao Paulo, BrazilLuciana Midori InuzukaDepartment of Neurology, University of Sao Paulo School of Medicine, Sao Paulo, BrazilLuciana Midori Inuzuka & Fernando KokDepartment of Pediatrics, Fukuoka Sanno Hospital, Fukuoka, JapanAtsushi IshiiDivision of Brain Sciences, Imperial College London, London, UKMichael R. JohnsonKuopio Epilepsy Center, Neurocenter, Kuopio University Hospital, Kuopio, FinlandReetta Kälviäinen & Anni SaarelaInstitute of Clinical Medicine, University of Eastern Finland, Kuopio, FinlandReetta Kälviäinen, Anni Saarela & Oskari TimonenDepartment of Child Neurology, Medical School, Kocaeli University, Kocaeli, TurkeyBulent KaraNeuroscience Unit, KEMRI-Wellcome Trust Research Programme, Kilifi, KenyaSymon M. Kariuki & Charles R. J. C. NewtonDepartment of Public Health, Pwani University, Kilifi, KenyaSymon M. Kariuki & Charles R. J. C. NewtonDepartment of Psychiatry, University of Oxford, Oxford, UKSymon M. Kariuki & Charles R. J. C. NewtonDepartment of Pharmacology and Toxicology, American University of Beirut Faculty of Medicine, Beirut, LebanonNathalie Khoueiry-ZgheibDepartment of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, CanadaKarl Martin Klein & Samuel WiebeDepartment of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, CanadaKarl Martin KleinHotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, CanadaKarl Martin Klein & Samuel WiebeAlberta Children’s Hospital Research Institute, University of Calgary, Calgary, Alberta, CanadaKarl Martin KleinEpilepsy Center Frankfurt Rhine-Main, Center of Neurology and Neurosurgery, Goethe University Frankfurt, Frankfurt, GermanyKarl Martin Klein, Felix Rosenow, Susanne Schubert-Bast, Adam Strzelczyk & Sophie von BrauchitschLOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe University Frankfurt, Frankfurt, GermanyKarl Martin Klein, Susanne Knake, Felix Rosenow, Susanne Schubert-Bast, Adam Strzelczyk, Sophie von Brauchitsch & Felix ZahnertNeuropediatric Clinic and Clinic for Neurorehabilitation, Epilepsy Center for Children and Adolescents, Vogtareuth, GermanyGerhard KlugerResearch Institute Rehabilitation / Transition, / Palliation, PMU Salzburg, Salzburg, AustriaGerhard KlugerEpilepsy Center Hessen-Marburg, Department of Neurology, Philipps University Marburg, Marburg, GermanySusanne Knake, Felix Rosenow, Adam Strzelczyk, Sophie von Brauchitsch & Felix ZahnertMendelics Genomic Analysis, São Paulo, BrazilFernando KokDepartment of Neuropediatrics and Muscular Disorders, University Medical Center, University of Freiburg, Freiburg, GermanyRudolf KorinthenbergCyprus Institute of Neurology and Genetics, Nicosia, CyprusAndreas Koupparis, Ioanna Kousiappa, Savvas S. Papacostas & George A. TantelesDepartment of Neurology, Medical University of Vienna, Vienna, AustriaMartin Krenn, Eva Reinthaler & Fritz ZimprichDepartment of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, SwitzerlandHeinz Krestel & Christoph J. SchankinInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, GermanyIlona Krey & Johannes R. LemkeInstitute of Experimental Epileptology and Cognition Research, Medical Faculty, University of Bonn, Bonn, GermanyWolfram S. Kunz & Gábor ZsurkaBonifatius Hospital Lingen, Neuropediatrics Wilhelmstrasse 13, Lingen, GermanyGerhard KurlemannDepartment of Neurology, Hofstra-Northwell Medical School, New York, NY, USARuben I. KuznieckyDepartment of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, ChinaPatrick KwanNeurophysiopatology and Movement Disorders Clinic, University of Messina, Messina, ItalyAngelo LabateDepartment of Paediatric Neurology, 2nd Faculty of Medicine, Charles University and Motol Hospital, Prague, Czech RepublicPetra Laššuthová, Lucie Sedláčková, Katalin Štěrbová & Markéta VlčkováFolkhälsan Research Center, Helsinki, FinlandAnna-Elina LehesjokiMedicum, University of Helsinki, Helsinki, FinlandAnna-Elina LehesjokiDepartment of Medical Genetics, Hospices Civils de Lyon and University of Lyon, Lyon, FranceGaetan LescaTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UKDavid Lewis-SmithDepartment of Clinical Neurosciences, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UKDavid Lewis-SmithDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hum, Hong Kong, ChinaGloria Hoi-Yee LiChild Neurology, New Children’s Hospital, Helsinki, FinlandTarja LinnankiviPediatric Research Center, University of Helsinki, Helsinki, FinlandTarja LinnankiviHelsinki University Hospital, Helsinki, FinlandTarja LinnankiviDepartment of Pediatrics and Neurology, Nationwide Children’s Hospital, Columbus, OH, USAWarren LoCitizens United for Research in Epilepsy, Chicago, IL, USALaura LubbersDepartment of Medicine, Tseung Kwan O Hospital, Hong Kong, ChinaColin H. T. LuiDepartment of Biology, Institute of Biological Sciences and Center for Study on Human Genome, University of São Paulo, São Paulo, BrazilLucia Inês Macedo-SouzaDepartment of Pediatrics, Filderklinik, Filderstadt, GermanyRene MadeleynUnit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, ItalyStefania MagriNeurology Department, University Hospital of Nancy, UMR 7039, CNRS, Lorraine University, Nancy, FranceLouis MaillardDepartment of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UKAnthony G. MarsonThe Emmes Company, Rockville, MD, USAAbigail G. MatthewsEpilepsy Center Kleinwachau, Radeberg, GermanyThomas MayerPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UKWendy McArdle, Samuel Neaves, Kate Northstone, Susan M. Ring & Nicholas John TimpsonDepartment of Genetics, Harvard Medical School, Boston, MA, USASteven M. McCarrollDepartment of Neurology, Boston Children’s Health Physicians, Maria Fareri Children’s Hospital at Westchester Medical Center, New York Medical College, New York, NY, USAPatricia McGoldrick & Steven M. WolfStanford University, Palo Alto, CA, USAKimford J. MeadorDepartment of Neurology, Hôpital Pellegrin, Bordeaux, FranceVéronique MichelNeurology, Northwestern University, Chicago, IL, USAJohn J. MillichapEpilepsy Center for Children, University Hospital Ruppin-Brandenburg, Brandenburg Medical School, Neuruppin, GermanyKaren Müller-SchlüterMRC Integrative Epidemiology Unit at University of Bristol, Bristol, UKSamuel Neaves, Susan M. Ring & Nicholas John TimpsonPediatric Neurology, University of Giessen, Giessen, GermanyBernd A. NeubauerDepartment of Psychiatry, University of Cape Town, Cape Town, South AfricaCharles R. J. C. NewtonKintampo Health Research Centre, Ghana Health Service, Kintampo, GhanaSeth Owusu-AgyeiUniversity of Health and Allied Science in Ho, Volta Region, GhanaSeth Owusu-AgyeiIstanbul University-Cerrahpaşa, Cerrahpaşa Medical Faculty, Department of Neurology, Istanbul, TurkeyÇiğdem ÖzkaraInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, FinlandAarno PalotieDepartments of Psychiatry, Rutgers University, Robert Wood Johnson Medical School and New Jersey Medical School, New Brunswick, NJ, USACarlos Pato & Michele PatoDepartment of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, NY, USACarlos Pato & Michele PatoUniversity of Pittsburgh, Pittsburgh, PA, USAPage B. PennellCentre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UKSlavé PetrovskiDepartment of Neurology, Morriston Hospital, Swansea Bay University Bay Health Board, Swansea, UKWilliam O. Pickrell & Robert H. W. PowellEpilepsy Genetics Program, Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children’s Hospital, Boston, MA, USARebecca Pinsky, Annapurna Poduri, Catherine Shain & Beth R. ShiedleyDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USADalila Pinto & Byron Ramirez-HamouzDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USADalila Pinto & Byron Ramirez-HamouzDepartment of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Amsterdam, Amsterdam, the NetherlandsDanielle PosthumaDepartment of Neurology, Gardner Neuroscience Institute, University of Cincinnati Medical Center, Cincinnati, OH, USAMichael PriviteraDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, GermanyAndreas ReifDepartment of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Würzburg, Würzburg, GermanyAndreas ReifDepartment of Functional Neurology and Epileptology, Hospices Civils de Lyon and University of Lyon, Lyon, FranceSylvain RheimsLyon’s Neuroscience Research Center, INSERM U1028 / CNRS UMR 5292, Lyon, FranceSylvain RheimsDepartment of Clinical Neurosciences, Centre Hospitalo-Universitaire Vaudois, Lausanne, SwitzerlandPhilippe RyvlinDepartments of Neurology, Beth Israel Deaconess Medical Center, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USASteven SchachterInstitute of Human Genetics, Bern University Hospital, Bern, SwitzerlandAndré SchallerDepartment of Neurology, Ludwig Maximilians University, Munich, GermanyChristoph J. SchankinFlorey and Murdoch Children’s Research Institutes, Parkville, Victoria, AustraliaIngrid E. SchefferDepartment of Paediatrics, The University of Melbourne, Royal Children’s Hospital, Parkville, Victoria, AustraliaIngrid E. SchefferDepartment of Neuropediatrics, Children’s Hospital, Goethe University Frankfurt, Frankfurt, GermanySusanne Schubert-BastDepartment of Epileptology, University Hospital Freiburg, Freiburg, GermanyAndreas Schulze-BonhageMedical School, Nova Southeastern University, Fort Lauderdale, FL, USAS. Anthony SienaSchool of Life Sciences, University of Glasgow, Glasgow, UKGraeme J. SillsPsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USAJordan W. SmollerDepartment of Psychiatry, Harvard Medical School, Boston, MA, USAJordan W. SmollerDivision of Neuropsychiatry, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USAGianfranco SpallettaDepartment of Neurology and Comprehensive Epilepsy Center, Thomas Jefferson University, Philadelphia, PA, USAMichael R. SperlingEpilepsy Center Kork, Kehl-Kork, GermanyBernhard J. SteinhoffDepartment of Neurodevelopmental Disorder Genetics, Institute of Brain Science, Nagoya City University Graduate School of Medical Science, Nagoya, Aichi, JapanToshimitsu Suzuki & Kazuhiro YamakawaLaboratory for Neurogenetics, RIKEN Center for Brain Science, Wako, Saitama, JapanToshimitsu Suzuki & Kazuhiro YamakawaCentre for Medical Genetics, Vilnius University Hospital Santaros Klinikos, Vilnius, LithuaniaBirute Tumiene & Algirdas UtkusInstitute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, LithuaniaBirute Tumiene & Algirdas UtkusDepartment of Child Neurology, Medical School, Marmara University, Istanbul, TurkeyDilsad TurkdoganDepartment of Neurology, UMR 5549, CNRS, Toulouse University Hospital, University of Toulouse, Toulouse, FranceLuc ValtonDRK-Northern German Epilepsy Centre for Children and Adolescents, Schwentinental-Raisdorf, GermanySarah von SpiczakMRC/Wits Rural Public Health & Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaRyan G. WagnerDepartment of Epidemiology and Global Health, Umeå University, Umeå, SwedenRyan G. WagnerDepartment of Clinical Sciences, Neurosciences, Umeå University, Umeå, SwedenRyan G. WagnerDepartment of Neurology and Epileptology, University of Aachen, Aachen, GermanyYvonne G. Weber & Stefan WolkingO’Brien Institute for Public Health, University of Calgary, Calgary, Alberta, CanadaSamuel WiebeClinical Research Unit, Cumming School of Medicine, University of Calgary, Calgary, Alberta, CanadaSamuel WiebeDepartment of Pediatric Neurology, Vivantes Hospital Neukölln, Berlin, GermanyMarkus WolffDepartment of Child Neurology, Medical School, Dokuz Eylul University, Izmir, TurkeyUluc YisStanley Division of Developmental Neurovirology, Johns Hopkins University, Baltimore, MD, USARobert YolkenBezmialem Vakif University, Institute of Life Sciences and Biotechnology, Istanbul, TurkeyEmrah YücesanAll authors contributed to patient phenotyping data and sample collection or to analyses. Roles in specific committees of the project are listed in the supplementary materials.

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