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
1
iPSYCH -
The Lundbeck Foundation Initiative for Integrative Psychiatric Research
2 Aarhus University [Aarhus]
3 Massachusetts General Hospital [Boston]
4 HMS - Harvard Medical School [Boston]
5 BROAD INSTITUTE - Broad Institute of MIT and Harvard
6 Charité - UniversitätsMedizin = Berlin University Medicine
7 JMU - Julius-Maximilians-Universität Würzburg = University of Würzburg [Würsburg, Germany]
8 Karolinska Institute
9 UNC - University of North Carolina [Chapel Hill]
10 UiO - University of Oslo
11 Oslo University Hospital [Oslo]
12 Cardiff University
13 MSSM - Icahn School of Medicine at Mount Sinai [New York]
14 Statens Serum Institut [Copenhagen]
15 Massachusetts General Hospital [Boston, MA, USA]
16 Karolinska Institutet [Stockholm]
17 University of Pittsburgh School of Medicine
18 ICM - Institut du Cerveau = Paris Brain Institute
2 Aarhus University [Aarhus]
3 Massachusetts General Hospital [Boston]
4 HMS - Harvard Medical School [Boston]
5 BROAD INSTITUTE - Broad Institute of MIT and Harvard
6 Charité - UniversitätsMedizin = Berlin University Medicine
7 JMU - Julius-Maximilians-Universität Würzburg = University of Würzburg [Würsburg, Germany]
8 Karolinska Institute
9 UNC - University of North Carolina [Chapel Hill]
10 UiO - University of Oslo
11 Oslo University Hospital [Oslo]
12 Cardiff University
13 MSSM - Icahn School of Medicine at Mount Sinai [New York]
14 Statens Serum Institut [Copenhagen]
15 Massachusetts General Hospital [Boston, MA, USA]
16 Karolinska Institutet [Stockholm]
17 University of Pittsburgh School of Medicine
18 ICM - Institut du Cerveau = Paris Brain Institute
Jakob Grove
- Function : Author
- PersonId : 1175864
- ORCID : 0000-0003-2284-5744
Thomas Als
- Function : Author
- PersonId : 1381071
- ORCID : 0000-0002-2963-1928
Raymond Walters
- Function : Author
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Hyejung Won
- Function : Author
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Esben Agerbo
- Function : Author
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Ole Andreassen
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Jonas Bybjerg-Grauholm
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Jane Christensen
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Ditte Demontis
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Srdjan Djurovic
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Ashley Dumont
- Function : Author
Jacqueline Goldstein
- Function : Author
Christine Hansen
- Function : Author
- PersonId : 1381076
- ORCID : 0000-0002-7518-4663
Mads Engel Hauberg
- Function : Author
Mads Hollegaard
- Function : Author
Sigrun Hope
- Function : Author
Daniel Howrigan
- Function : Author
- PersonId : 1381077
- ORCID : 0000-0002-7721-4838
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
- Function : Author
- PersonId : 1381078
- ORCID : 0000-0002-2967-6624
Terje Nærland
- Function : Author
- PersonId : 1381079
- ORCID : 0000-0001-9175-4286
Duncan Palmer
- Function : Author
Aarno Palotie
- Function : Author
Carsten Bøcker Pedersen
- Function : Author
- PersonId : 1381080
- ORCID : 0000-0003-2077-8533
Marianne Giørtz Pedersen
- Function : Author
Timothy Dpoterba
- Function : Author
Beate St Pourcain
- Function : Author
- PersonId : 1188328
- ORCID : 0000-0002-4680-3517
Per Qvist
- Function : Author
- PersonId : 1381081
- ORCID : 0000-0002-0750-0089
Karola Rehnström
- Function : Author
Abraham Reichenberg
- Function : Author
Jennifer Reichert
- Function : Author
Elise Robinson
- Function : Author
Kathryn Roeder
- Function : Author
Panos Roussos
- Function : Author
Evald Saemundsen
- Function : Author
- PersonId : 1381082
- ORCID : 0000-0001-6912-5846
Sven Sandin
- Function : Author
F Kyle Satterstrom
- Function : Author
George Davey Smith
- Function : Author
- PersonId : 1183492
- ORCID : 0000-0002-1407-8314
Hreinn Stefansson
- Function : Author
Stacy Steinberg
- Function : Author
- PersonId : 1381083
- ORCID : 0000-0001-7726-5152
Christine Stevens
- Function : Author
Patrick Sullivan
- Function : Author
- PersonId : 763175
- ORCID : 0000-0002-6619-873X
Patrick Turley
- Function : Author
G Bragi Walters
- Function : Author
Xinyi Xu
- Function : Author
Kari Stefansson
- Function : Author
- PersonId : 1275004
- ORCID : 0000-0003-1676-864X
Daniel Geschwind
- Function : Author
- PersonId : 1175863
- ORCID : 0000-0003-2896-3450
Merete Nordentoft
- Function : Author
David Hougaard
- Function : Author
- PersonId : 1377322
- ORCID : 0000-0001-5928-3517
Thomas Werge
- Function : Author
- PersonId : 1159712
- ORCID : 0000-0003-1829-0766
Ole Mors
- Function : Author
Preben Bo Mortensen
- Function : Author
Benjamin Neale
- Function : Author
- PersonId : 1229344
- ORCID : 0000-0003-1513-6077
Mark Daly
- Function : Author
- PersonId : 1218126
- ORCID : 0000-0002-0949-8752
Anders Børglum
- Function : Author
- PersonId : 812342
- ORCID : 0000-0001-8627-7219
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
- Function : Author
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
- Function : Author
Ian B Hickie
- Function : Author
Per Hoffmann
- Function : Author
Georg Homuth
- Function : Author
Carsten Horn
- Function : Author
Jouke-Jan Hottenga
- Function : Author
Marcus Ising
- Function : Author
Rick Jansen
- Function : Author
Eric Jorgenson
- Function : Author
James A Knowles
- Function : Author
Isaac S Kohane
- Function : Author
Julia Kraft
- Function : Author
Warren W Kretzschmar
- Function : Author
Jesper Krogh
- Function : Author
Zoltán Kutalik
- Function : Author
Yihan Li
- Function : Author
Penelope A Lind
- Function : Author
Donald J Macintyre
- Function : Author
Dean F Mackinnon
- Function : Author
Robert M Maier
- Function : Author
Wolfgang Maier
- Function : Author
Jonathan Marchini
- Function : Author
Hamdi Mbarek
- Function : Author
Patrick Mcgrath
- Function : Author
Peter Mcguffin
- Function : Author
Sarah E Medland
- Function : Author
Divya Mehta
- Function : Author
Christel M Middeldorp
- Function : Author
Evelin Mihailov
- Function : Author
Yuri Milaneschi
- Function : Author
Lili Milani
- Function : Author
Francis M Mondimore
- Function : Author
Grant W Montgomery
- Function : Author
Sara Mostafavi
- Function : Author
Niamh Mullins
- Function : Author
Matthias Nauck
- Function : Author
Bernard Ng
- Function : Author
Michel G Nivard
- Function : Author
Dale R Nyholt
- Function : Author
Paul F O'Reilly
- Function : Author
Hogni Oskarsson
- Function : Author
Michael J Owen
- Function : Author
Jodie N Painter
- Function : Author
Roseann E Peterson
- Function : Author
Erik Pettersson
- Function : Author
Wouter J Peyrot
- Function : Author
Giorgio Pistis
- Function : Author
Danielle Posthuma
- Function : Author
Jorge A Quiroz
- Function : Author
John P Rice
- Function : Author
Brien P Riley
- Function : Author
Margarita Rivera
- Function : Author
Saira Saeed Mirza
- Function : Author
Robert Schoevers
- Function : Author
Eva C Schulte
- Function : Author
Ling Shen
- Function : Author
Jianxin Shi
- Function : Author
Stanley I Shyn
- Function : Author
Engilbert Sigurdsson
- Function : Author
Grant C B Sinnamon
- Function : Author
Johannes H Smit
- Function : Author
Daniel J Smith
- Function : Author
Fabian Streit
- Function : Author
Jana Strohmaier
- Function : Author
Katherine E Tansey
- Function : Author
Henning Teismann
- Function : Author
Alexander Teumer
- Function : Author
Wesley Thompson
- Function : Author
Pippa A Thomson
- Function : Author
Thorgeir E Thorgeirsson
- Function : Author
Matthew Traylor
- Function : Author
Jens Treutlein
- Function : Author
Vassily Trubetskoy
- Function : Author
André G Uitterlinden
- Function : Author
Daniel Umbricht
- Function : Author
Sandra van Der Auwera
- Function : Author
Albert M Van Hemert
- Function : Author
Alexander Viktorin
- Function : Author
Peter M Visscher
- Function : Author
Yunpeng Wang
- Function : Author
Bradley T Webb
- Function : Author
Shantel Marie Weinsheimer
- Function : Author
Jürgen Wellmann
- Function : Author
Gonneke Willemsen
- Function : Author
Stephanie H Witt
- Function : Author
Yang Wu
- Function : Author
Hualin S Xi
- Function : Author
Jian Yang
- Function : Author
Futao Zhang
- Function : Author
Volker Arolt
- Function : Author
Bernhard T Baune
- Function : Author
Klaus Berger
- Function : Author
Dorret I Boomsma
- Function : Author
Sven Cichon
- Function : Author
Udo Dannlowski
- Function : Author
E J C De Geus
- Function : Author
J Raymond Depaulo
- Function : Author
Enrico Domenici
- Function : Author
Katharina Domschke
- Function : Author
Tõnu Esko
- Function : Author
Hans J Grabe
- Function : Author
Steven P Hamilton
- Function : Author
Caroline Hayward
- Function : Author
Andrew C Heath
- Function : Author
Kenneth S Kendler
- Function : Author
Stefan Kloiber
- Function : Author
Glyn Lewis
- Function : Author
Qingqin S Li
- Function : Author
Susanne Lucae
- Function : Author
Pamela a F Madden
- Function : Author
Patrik K Magnusson
- Function : Author
Nicholas G Martin
- Function : Author
Andrew M Mcintosh
- Function : Author
Andres Metspalu
- Function : Author
Bertram Müller-Myhsok
- Function : Author
Markus M Nöthen
- Function : Author
Michael C O'Donovan
- Function : Author
Sara A Paciga
- Function : Author
Nancy L Pedersen
- Function : Author
Brenda W J H Penninx
- Function : Author
Roy H Perlis
- Function : Author
David J Porteous
- Function : Author
James B Potash
- Function : Author
Martin Preisig
- Function : Author
Marcella Rietschel
- Function : Author
Catherine Schaefer
- Function : Author
Thomas G Schulze
- Function : Author
Jordan W Smoller
- Function : Author
Henning Tiemeier
- Function : Author
Rudolf Uher
- Function : Author
Henry Völzke
- Function : Author
Myrna M Weissman
- Function : Author
Cathryn M Lewis
- Function : Author
Douglas F Levinson
- Function : Author
Gerome Breen
- Function : Author
Michelle Agee
- Function : Author
Babak Alipanahi
- Function : Author
Adam Auton
- Function : Author
Robert K Bell
- Function : Author
Katarzyna Bryc
- Function : Author
Sarah L Elson
- Function : Author
Pierre Fontanillas
- Function : Author
Nicholas A Furlotte
- Function : Author
Bethann S Hromatka
- Function : Author
Karen E Huber
- Function : Author
Aaron Kleinman
- Function : Author
Nadia K Litterman
- Function : Author
Matthew H Mcintyre
- Function : Author
Joanna L Mountain
- Function : Author
Elizabeth S Noblin
- Function : Author
Carrie a M Northover
- Function : Author
Steven J Pitts
- Function : Author
J Fah Sathirapongsasuti
- Function : Author
Olga V Sazonova
- Function : Author
Janie F Shelton
- Function : Author
Suyash Shringarpure
- Function : Author
Joyce Y Tung
- Function : Author
Vladimir Vacic
- Function : Author
Catherine H Wilson
- Function : Author
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.