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Journal Articles Nature Genetics Year : 2019

Identification of common genetic risk variants for autism spectrum disorder

Jakob Grove (1, 2) , Stephan Ripke (3, 4, 5, 6) , Thomas Als (1, 2) , Manuel Mattheisen (1, 2, 7, 8) , Raymond Walters (3, 4, 5) , Hyejung Won (9) , Jonatan Pallesen (1, 2) , Esben Agerbo (1, 2) , Ole Andreassen (10, 11) , Richard Anney (12) , Swapnil Awashti (6) , Rich Belliveau (5) , Francesco Bettella (10, 11) , Joseph Buxbaum (13) , Jonas Bybjerg-Grauholm (1, 14) , Marie Bækvad-Hansen (1, 14) , Felecia Cerrato (5) , Kimberly Chambert (5) , Jane Christensen (1, 2) , Claire Churchhouse (15, 5) , Karin Dellenvall (16) , Ditte Demontis (1, 2) , Silvia De Rubeis (13) , Bernie Devlin (17) , Srdjan Djurovic (10, 11) , Ashley Dumont , Jacqueline Goldstein , Christine Hansen , Mads Engel Hauberg , Mads Hollegaard , Sigrun Hope , Daniel Howrigan , Hailiang Huang , Christina Hultman , Lambertus Klei , Julian Maller , Joanna Martin , Alicia Martin , Jennifer Moran , Mette Nyegaard , Terje Nærland , Duncan Palmer , Aarno Palotie , Carsten Bøcker Pedersen , Marianne Giørtz Pedersen , Timothy Dpoterba , Jesper Buchhave Poulsen (1) , Beate St Pourcain , Per Qvist , Karola Rehnström , Abraham Reichenberg , Jennifer Reichert , Elise Robinson , Kathryn Roeder , Panos Roussos , Evald Saemundsen , Sven Sandin , F Kyle Satterstrom , George Davey Smith , Hreinn Stefansson , Stacy Steinberg , Christine Stevens , Patrick Sullivan , Patrick Turley , G Bragi Walters , Xinyi Xu , Kari Stefansson , Daniel Geschwind , Merete Nordentoft , David Hougaard , Thomas Werge , Ole Mors , Preben Bo Mortensen , Benjamin Neale , Mark Daly , Anders Børglum , Naomi R Wray , Maciej Trzaskowski , Enda M Byrne , Abdel Abdellaoui , Mark J Adams , Tracy M Air , Till F M Andlauer , Silviu-Alin Bacanu , Aartjan T F Beekman , Tim B Bigdeli , Elisabeth B Binder , Douglas H R Blackwood , Julien Bryois , Henriette N Buttenschøn , Na Cai , Enrique Castelao , Toni-Kim Clarke , Jonathan R I Coleman , Lucía Colodro-Conde , Baptiste Couvy-Duchesne (18) , Nick Craddock , Gregory E Crawford , Gail Davies , Ian J Deary , Franziska Degenhardt , Eske M Derks , Nese Direk , Conor V Dolan , Erin C Dunn , Thalia C Eley , Valentina Escott-Price , Farnush Farhadi Hassan Kiadeh , Hilary K Finucane , Andreas J Forstner , Josef Frank , Héléna A Gaspar , Michael Gill , Fernando S Goes , Scott D Gordon , Lynsey S Hall , Thomas F Hansen , Stefan Herms , Ian B Hickie , Per Hoffmann , Georg Homuth , Carsten Horn , Jouke-Jan Hottenga , Marcus Ising , Rick Jansen , Eric Jorgenson , James A Knowles , Isaac S Kohane , Julia Kraft , Warren W Kretzschmar , Jesper Krogh , Zoltán Kutalik , Yihan Li , Penelope A Lind , Donald J Macintyre , Dean F Mackinnon , Robert M Maier , Wolfgang Maier , Jonathan Marchini , Hamdi Mbarek , Patrick Mcgrath , Peter Mcguffin , Sarah E Medland , Divya Mehta , Christel M Middeldorp , Evelin Mihailov , Yuri Milaneschi , Lili Milani , Francis M Mondimore , Grant W Montgomery , Sara Mostafavi , Niamh Mullins , Matthias Nauck , Bernard Ng , Michel G Nivard , Dale R Nyholt , Paul F O'Reilly , Hogni Oskarsson , Michael J Owen , Jodie N Painter , Roseann E Peterson , Erik Pettersson , Wouter J Peyrot , Giorgio Pistis , Danielle Posthuma , Jorge A Quiroz , John P Rice , Brien P Riley , Margarita Rivera , Saira Saeed Mirza , Robert Schoevers , Eva C Schulte , Ling Shen , Jianxin Shi , Stanley I Shyn , Engilbert Sigurdsson , Grant C B Sinnamon , Johannes H Smit , Daniel J Smith , Fabian Streit , Jana Strohmaier , Katherine E Tansey , Henning Teismann , Alexander Teumer , Wesley Thompson , Pippa A Thomson , Thorgeir E Thorgeirsson , Matthew Traylor , Jens Treutlein , Vassily Trubetskoy , André G Uitterlinden , Daniel Umbricht , Sandra van Der Auwera , Albert M Van Hemert , Alexander Viktorin , Peter M Visscher , Yunpeng Wang , Bradley T Webb , Shantel Marie Weinsheimer , Jürgen Wellmann , Gonneke Willemsen , Stephanie H Witt , Yang Wu , Hualin S Xi , Jian Yang , Futao Zhang , Volker Arolt , Bernhard T Baune , Klaus Berger , Dorret I Boomsma , Sven Cichon , Udo Dannlowski , E J C De Geus , J Raymond Depaulo , Enrico Domenici , Katharina Domschke , Tõnu Esko , Hans J Grabe , Steven P Hamilton , Caroline Hayward , Andrew C Heath , Kenneth S Kendler , Stefan Kloiber , Glyn Lewis , Qingqin S Li , Susanne Lucae , Pamela a F Madden , Patrik K Magnusson , Nicholas G Martin , Andrew M Mcintosh , Andres Metspalu , Bertram Müller-Myhsok , Markus M Nöthen , Michael C O'Donovan , Sara A Paciga , Nancy L Pedersen , Brenda W J H Penninx , Roy H Perlis , David J Porteous , James B Potash , Martin Preisig , Marcella Rietschel , Catherine Schaefer , Thomas G Schulze , Jordan W Smoller , Henning Tiemeier , Rudolf Uher , Henry Völzke , Myrna M Weissman , Cathryn M Lewis , Douglas F Levinson , Gerome Breen , Michelle Agee , Babak Alipanahi , Adam Auton , Robert K Bell , Katarzyna Bryc , Sarah L Elson , Pierre Fontanillas , Nicholas A Furlotte , Bethann S Hromatka , Karen E Huber , Aaron Kleinman , Nadia K Litterman , Matthew H Mcintyre , Joanna L Mountain , Elizabeth S Noblin , Carrie a M Northover , Steven J Pitts , J Fah Sathirapongsasuti , Olga V Sazonova , Janie F Shelton , Suyash Shringarpure , Joyce Y Tung , Vladimir Vacic , Catherine H Wilson
Hyejung Won
Richard Anney
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Ashley Dumont
  • Function : Author
Jacqueline Goldstein
  • Function : Author
Christine Hansen
Mads Engel Hauberg
  • Function : Author
Mads Hollegaard
  • Function : Author
Sigrun Hope
  • Function : Author
Daniel Howrigan
Hailiang Huang
  • Function : Author
Christina Hultman
  • Function : Author
Lambertus Klei
  • Function : Author
Julian Maller
  • Function : Author
Joanna Martin
  • Function : Author
Alicia Martin
  • Function : Author
Jennifer Moran
  • Function : Author
Mette Nyegaard
Terje Nærland
Duncan Palmer
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Aarno Palotie
  • Function : Author
Carsten Bøcker Pedersen
Marianne Giørtz Pedersen
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Timothy Dpoterba
  • Function : Author
Beate St Pourcain
Per Qvist
Karola Rehnström
  • Function : Author
Abraham Reichenberg
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Jennifer Reichert
  • Function : Author
Elise Robinson
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Kathryn Roeder
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Panos Roussos
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Evald Saemundsen
Sven Sandin
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F Kyle Satterstrom
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George Davey Smith
Hreinn Stefansson
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Stacy Steinberg
Christine Stevens
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Patrick Sullivan
Patrick Turley
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G Bragi Walters
  • Function : Author
Xinyi Xu
  • Function : Author
Kari Stefansson
Daniel Geschwind
Merete Nordentoft
  • Function : Author
David Hougaard
Thomas Werge
Ole Mors
  • Function : Author
Preben Bo Mortensen
  • Function : Author
Benjamin Neale
Mark Daly
Anders Børglum
Naomi R Wray
  • Function : Author
Maciej Trzaskowski
  • Function : Author
Enda M Byrne
  • Function : Author
Abdel Abdellaoui
  • Function : Author
Mark J Adams
  • Function : Author
Tracy M Air
  • Function : Author
Till F M Andlauer
  • Function : Author
Silviu-Alin Bacanu
  • Function : Author
Aartjan T F Beekman
  • Function : Author
Tim B Bigdeli
  • Function : Author
Elisabeth B Binder
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Douglas H R Blackwood
  • Function : Author
Julien Bryois
  • Function : Author
Henriette N Buttenschøn
  • Function : Author
Na Cai
  • Function : Author
Enrique Castelao
  • Function : Author
Toni-Kim Clarke
  • Function : Author
Jonathan R I Coleman
  • Function : Author
Lucía Colodro-Conde
  • Function : Author
Nick Craddock
  • Function : Author
Gregory E Crawford
  • Function : Author
Gail Davies
  • Function : Author
Ian J Deary
  • Function : Author
Franziska Degenhardt
  • Function : Author
Eske M Derks
  • Function : Author
Nese Direk
  • Function : Author
Conor V Dolan
  • Function : Author
Erin C Dunn
  • Function : Author
Thalia C Eley
  • Function : Author
Valentina Escott-Price
  • Function : Author
Farnush Farhadi Hassan Kiadeh
  • Function : Author
Hilary K Finucane
  • Function : Author
Andreas J Forstner
  • Function : Author
Josef Frank
  • Function : Author
Héléna A Gaspar
  • Function : Author
Michael Gill
  • Function : Author
Fernando S Goes
  • Function : Author
Scott D Gordon
  • Function : Author
Lynsey S Hall
  • Function : Author
Thomas F Hansen
  • Function : Author
Stefan Herms
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Ian B Hickie
  • Function : Author
Per Hoffmann
  • Function : Author
Georg Homuth
  • Function : Author
Carsten Horn
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Jouke-Jan Hottenga
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Marcus Ising
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Rick Jansen
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Eric Jorgenson
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James A Knowles
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Isaac S Kohane
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Julia Kraft
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Warren W Kretzschmar
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Jesper Krogh
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Zoltán Kutalik
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Yihan Li
  • Function : Author
Penelope A Lind
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Donald J Macintyre
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Dean F Mackinnon
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Robert M Maier
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Wolfgang Maier
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Jonathan Marchini
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Hamdi Mbarek
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Patrick Mcgrath
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Peter Mcguffin
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Sarah E Medland
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Divya Mehta
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Christel M Middeldorp
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Evelin Mihailov
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Yuri Milaneschi
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Lili Milani
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Francis M Mondimore
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Grant W Montgomery
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Sara Mostafavi
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Niamh Mullins
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Matthias Nauck
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Bernard Ng
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Michel G Nivard
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Dale R Nyholt
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Paul F O'Reilly
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Hogni Oskarsson
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Michael J Owen
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Jodie N Painter
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Roseann E Peterson
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Erik Pettersson
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Wouter J Peyrot
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Giorgio Pistis
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Danielle Posthuma
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Jorge A Quiroz
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John P Rice
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Brien P Riley
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Margarita Rivera
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Saira Saeed Mirza
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Robert Schoevers
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Eva C Schulte
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Ling Shen
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Jianxin Shi
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Stanley I Shyn
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Engilbert Sigurdsson
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Grant C B Sinnamon
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Johannes H Smit
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Daniel J Smith
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Fabian Streit
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Jana Strohmaier
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Katherine E Tansey
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Henning Teismann
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Alexander Teumer
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Wesley Thompson
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Pippa A Thomson
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Thorgeir E Thorgeirsson
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Matthew Traylor
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Jens Treutlein
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Vassily Trubetskoy
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André G Uitterlinden
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Daniel Umbricht
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Sandra van Der Auwera
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Albert M Van Hemert
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Alexander Viktorin
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Peter M Visscher
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Yunpeng Wang
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Bradley T Webb
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Shantel Marie Weinsheimer
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Jürgen Wellmann
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Gonneke Willemsen
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Stephanie H Witt
  • Function : Author
Yang Wu
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Hualin S Xi
  • Function : Author
Jian Yang
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Futao Zhang
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Volker Arolt
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Bernhard T Baune
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Klaus Berger
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Dorret I Boomsma
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Sven Cichon
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Udo Dannlowski
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E J C De Geus
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J Raymond Depaulo
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Enrico Domenici
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Katharina Domschke
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Tõnu Esko
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Hans J Grabe
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Steven P Hamilton
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Caroline Hayward
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Andrew C Heath
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Kenneth S Kendler
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Stefan Kloiber
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Glyn Lewis
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Qingqin S Li
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Susanne Lucae
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Pamela a F Madden
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Patrik K Magnusson
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Nicholas G Martin
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Andrew M Mcintosh
  • Function : Author
Andres Metspalu
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Bertram Müller-Myhsok
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Markus M Nöthen
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Michael C O'Donovan
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Sara A Paciga
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Nancy L Pedersen
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Brenda W J H Penninx
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Roy H Perlis
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David J Porteous
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James B Potash
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Martin Preisig
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Marcella Rietschel
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Catherine Schaefer
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Thomas G Schulze
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Jordan W Smoller
  • Function : Author
Henning Tiemeier
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Rudolf Uher
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Henry Völzke
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Myrna M Weissman
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Cathryn M Lewis
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Douglas F Levinson
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Gerome Breen
  • Function : Author
Michelle Agee
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Babak Alipanahi
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Adam Auton
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Robert K Bell
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Katarzyna Bryc
  • Function : Author
Sarah L Elson
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Pierre Fontanillas
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Nicholas A Furlotte
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Bethann S Hromatka
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Karen E Huber
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Aaron Kleinman
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Nadia K Litterman
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Matthew H Mcintyre
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Joanna L Mountain
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Elizabeth S Noblin
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Carrie a M Northover
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Steven J Pitts
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J Fah Sathirapongsasuti
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Olga V Sazonova
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Janie F Shelton
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Suyash Shringarpure
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Joyce Y Tung
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Vladimir Vacic
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Catherine H Wilson
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Abstract

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.

Dates and versions

hal-04570541 , version 1 (07-05-2024)

Identifiers

Cite

Jakob Grove, Stephan Ripke, Thomas Als, Manuel Mattheisen, Raymond Walters, et al.. Identification of common genetic risk variants for autism spectrum disorder. Nature Genetics, 2019, 51 (3), pp.431-444. ⟨10.1038/s41588-019-0344-8⟩. ⟨hal-04570541⟩
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