Authors

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, Thomas Jefferson UniversityFollow
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 de Haan
Peter De Jonghe
Carolien G.F. de Kovel
Norman Delanty
Chantal Depondt
Orrin Devinsky
Dennis J. Dlugos
Colin P. Doherty
Christian E. Elger
Johan G. Eriksson
Thomas N. Ferraro
Martha Feuch
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
Bobby P.C. Koeleman
Roland Krause
Martin Krenn
Wolfram S. Kunz
Ruben Kuzniecky
Patrick Kwan
Dennis Lal
Yu-Lung Lau
Anna-Elina Lehesjoki
Holger Lerche
Costin Leu
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
Palotie 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
Alexander Smith
David F. Smith
Michael C. Smith
Philip E. Smith
Anja C.M. Sonsma
Doug Speed
Michael R. Sperling, Thomas Jefferson UniversityFollow
Bernhard J. Steinhoff
Ulrich Stephani
Remi Stevelink
Konstantin Strauch
Pasquale Striano
Hans Stroink
Rainer Surges
K. Meng Tan
Liu Lin Thio
G. Neil Thomas
Marian Todaro
Rossana Tozzi
Maria S. Vari
Ellen P.G. Vining
Frank Visscher
Sarah von Spiczak
Nicole M. Walley
Yvonne G. Weber
Zhi Wei
Judith Weisenberg
Christopher D. Whelan
Peter Widdess-Walsh
Markus Wolff
Wolking Wolking
Wanling Yang
Federico Zara
Fritz Zimprich

Document Type

Article

Publication Date

12-10-2018

Comments

This article has been peer reviewed. It is the author’s final published version in Nature Communications, Volume 9, Issue 1, December 2018, Article number 5269.

The published version is available at https://doi.org/10.1038/s41467-018-07524-z. Copyright © Abou-Khalil et al.

Abstract

The epilepsies affect around 65 million people worldwide and have a substantial missing heritability component. We report a genome-wide mega-analysis involving 15,212 individuals with epilepsy and 29,677 controls, which reveals 16 genome-wide significant loci, of which 11 are novel. Using various prioritization criteria, we pinpoint the 21 most likely epilepsy genes at these loci, with the majority in genetic generalized epilepsies. These genes have diverse biological functions, including coding for ion-channel subunits, transcription factors and a vitamin-B6 metabolism enzyme. Converging evidence shows that the common variants associated with epilepsy play a role in epigenetic regulation of gene expression in the brain. The results show an enrichment for monogenic epilepsy genes as well as known targets of antiepileptic drugs. Using SNP-based heritability analyses we disentangle both the unique and overlapping genetic basis to seven different epilepsy subtypes. Together, these findings provide leads for epilepsy therapies based on underlying pathophysiology.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

30531953

Language

English

Included in

Neurology Commons

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