Abstract

Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways.

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Acknowledgements

We thank S. Hyman and R. Hosking for their thoughtful comments. We also thank A. Pai for his help in the development of the pTDT analytic software. E.B.R. and D.J.W. were funded by National Institute of Mental Health grant 1K01MH099286-01A1 and Brain Behavior Research Foundation (NARSAD) Young Investigator grant 22379. E.M.W. was funded by the Stanley Center for Psychiatric Research at the Broad Institute. A.O. was funded by an ERC Consolidator Grant (647648 EdGe). We thank the families who took part in the Simons Simplex Collection study and the clinicians who collected data at each of the study sites. The iPSYCH project is funded by the Lundbeck Foundation and the universities and university hospitals of Aarhus and Copenhagen. Genotyping of iPSYCH and PGC samples was supported by grants from the Stanley Foundation, the Simons Foundation (SFARI 311789 to M.J.D.), and the National Institute of Mental Health (5U01MH094432-02 to M.J.D.). This work was also supported by a grant from the Simons Foundation (SFARI 402281 to S.J.S.). The authors would like to thank the Exome Aggregation Consortium and the groups that provided exome variant data for comparison. A full list of contributing groups can be found on the ExAC website (see URLs).

Author information

Affiliations

  1. Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

    • Daniel J Weiner
    • , Emilie M Wigdor
    • , Stephan Ripke
    • , Raymond K Walters
    • , Jack A Kosmicki
    • , Kaitlin E Samocha
    • , Jacqueline I Goldstein
    • , Jacob Taylor
    • , Daniel Howrigan
    • , Timothy Poterba
    • , Verneri Anttila
    • , Hailiang Huang
    • , Phil H Lee
    • , Benjamin Neale
    • , Mark J Daly
    •  & Elise B Robinson
  2. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

    • Daniel J Weiner
    • , Emilie M Wigdor
    • , Stephan Ripke
    • , Raymond K Walters
    • , Jack A Kosmicki
    • , Kaitlin E Samocha
    • , Jacqueline I Goldstein
    • , Jacob Taylor
    • , Ashley Dumont
    • , Daniel Howrigan
    • , Jennifer Moran
    • , Timothy Poterba
    • , Christine Stevens
    • , Verneri Anttila
    • , Hailiang Huang
    • , Phil H Lee
    • , Benjamin Neale
    • , Mark J Daly
    •  & Elise B Robinson
  3. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

    • Daniel J Weiner
    • , Emilie M Wigdor
    • , Stephan Ripke
    • , Jack A Kosmicki
    • , Kaitlin E Samocha
    • , Jacqueline I Goldstein
    • , Jacob Taylor
    • , Daniel Howrigan
    • , Timothy Poterba
    • , Mark J Daly
    •  & Elise B Robinson
  4. Department of Psychiatry and Psychotherapy, Charité, Campus Mitte, Berlin, Germany.

    • Stephan Ripke
  5. Program in Genetics and Genomics, Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts, USA.

    • Jack A Kosmicki
    •  & Christopher A Walsh
  6. Department of Biomedicine (Human Genetics), Aarhus University, Aarhus, Denmark.

    • Jakob Grove
    • , Manuel Mattheisen
    • , Preben Bo Mortensen
    •  & Anders D Børglum
  7. Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark.

    • Jakob Grove
    • , Jonas Bybjerg-Grauholm
    • , Thomas Werge
    • , Marie Bækvad-Hansen
    • , Christine Hansen
    • , Thomas F Hansen
    • , Manuel Mattheisen
    • , Ole Mors
    • , Merete Nordentoft
    • , Bent Nørgaard-Pedersen
    • , Jesper Poulsen
    • , Marianne G Pedersen
    • , Carsten B Pedersen
    • , Christine S Hansen
    • , Preben Bo Mortensen
    •  & Anders D Børglum
  8. Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.

    • Jakob Grove
    • , Manuel Mattheisen
    •  & Anders D Børglum
  9. Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.

    • Jakob Grove
  10. Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

    • Aysu Okbay
  11. Danish Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.

    • Jonas Bybjerg-Grauholm
    • , David M Hougaard
    • , Marie Bækvad-Hansen
    • , Christine Hansen
    • , Bent Nørgaard-Pedersen
    • , Jesper Poulsen
    •  & Christine S Hansen
  12. Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Copenhagen, Denmark.

    • Thomas Werge
    •  & Thomas F Hansen
  13. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

    • Thomas Werge
  14. Department of Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • Jacob Taylor
  15. Behavioural Sciences Unit, Institute of Child Health, University College London, London, UK.

    • David Skuse
  16. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

    • Lambertus Klei
    • , Nancy Minshew
    •  & Bernie Devlin
  17. Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, Wales, UK.

    • Richard Anney
  18. Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.

    • Stephan J Sanders
    •  & Somer Bishop
  19. National Centre for Register-based Research, University of Aarhus, Aarhus, Denmark.

    • Marianne G Pedersen
    • , Carsten B Pedersen
    •  & Preben Bo Mortensen
  20. Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.

    • George Davey Smith
  21. Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.

    • Ole Mors
  22. Mental Health Services in the Capital Region of Denmark, Mental Health Center Copenhagen, University of Copenhagen, Copenhagen, Denmark.

    • Merete Nordentoft
  23. MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.

    • Peter Holmans
  24. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.

    • Phil H Lee
  25. Queensland Institute of Medical Research, Brisbane, Queensland, Australia.

    • Sarah E Medland
  26. Department of Psychiatry, University of California, San Francisco, San Francisco, California, USA.

    • Lauren A Weiss
    • , A Jeremy Willsey
    • , Kathryn Tsang
    • , Matthew W State
    • , Robert Hendren
    •  & Vanessa H Bal
  27. Institute of Human Genetics, University of California, San Francisco, San Francisco, California, USA.

    • Lauren A Weiss
    •  & Kathryn Tsang
  28. Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.

    • Lonnie Zwaigenbaum
  29. Division of Genetics, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA.

    • Timothy W Yu
    •  & Christopher A Walsh
  30. School of Education, University of Birmingham, Birmingham, UK.

    • Kerstin Wittemeyer
  31. Department of Medicine, University of Washington, Seattle, Washington, USA.

    • Ellen M Wijsman
  32. Department of Biostatistics, University of Washington, Seattle, Washington, USA.

    • Ellen M Wijsman
  33. Department of Psychiatry, Carver College of Medicine, Iowa City, Iowa, USA.

    • Thomas H Wassink
  34. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe University Frankfurt, Frankfurt am Main, Germany.

    • Regina Waltes
    • , Fritz Poustka
    • , Christine M Freitag
    • , Eftichia Duketis
    • , Andreas G Chiocchetti
    •  & Sven Bölte
  35. Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA.

    • Christopher A Walsh
  36. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.

    • Christopher A Walsh
  37. Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA.

    • Christopher A Walsh
  38. Department of Psychiatry, University of Oxford and Warneford Hospital, Oxford, UK.

    • Simon Wallace
    •  & Anthony J Bailey
  39. Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.

    • Jacob A S Vorstman
    • , Herman van Engeland
    •  & Maretha V De Jonge
  40. Battelle Center for Mathematical Medicine, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.

    • Veronica J Vieland
  41. Instituto Nacional de Saœde Dr. Ricardo Jorge, Lisboa, Portugal.

    • Astrid M Vicente
    • , Catarina T Correia
    •  & Inês C Conceição
  42. Center for Biodiversity, Functional and Integrative Genomics, Campus da FCUL, Lisboa, Portugal.

    • Astrid M Vicente
    • , Catarina T Correia
    •  & Inês C Conceição
  43. Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, Canada.

    • Ann P Thompson
  44. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.

    • Peter Szatmari
  45. Karolinska Institutet, Solna, Sweden.

    • Oscar Svantesson
    • , Bozenna Iliadou
    •  & Christina M Hultman
  46. deCODE Genetics, Reykjavik, Iceland.

    • Stacy Steinberg
    • , Kari Stefansson
    •  & Hreinn Stefansson
  47. Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Latha Soorya
    • , Jennifer Reichert
    • , Abraham Reichenberg
    • , Christopher S Poultney
    • , Dalila Pinto
    • , Alexander Kolevzon
    • , Silvia De Rubeis
    •  & Joseph D Buxbaum
  48. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Latha Soorya
    • , Jennifer Reichert
    • , Abraham Reichenberg
    • , Christopher S Poultney
    • , Dalila Pinto
    • , Alexander Kolevzon
    • , Dorothy E Grice
    • , Silvia De Rubeis
    •  & Joseph D Buxbaum
  49. Department of Psychiatry, Rush University Medical Center, Chicago, Illinois, USA.

    • Latha Soorya
  50. Department of Psychiatry and Drug Addiction, Tbilisi State Medical University, Tbilisi, Georgia.

    • Teimuraz Silagadze
  51. The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.

    • Stephen W Scherer
    •  & Andrew D Paterson
  52. McLaughlin Centre, University of Toronto, Toronto, Ontario, Canada.

    • Stephen W Scherer
  53. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

    • Stephen W Scherer
    •  & Andrew D Paterson
  54. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Gerard D Schellenberg
  55. State Diagnostic and Counseling Centre, Kopavogur, Iceland.

    • Sven Sandin
    •  & Evald Saemundsen
  56. Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.

    • Guy A Rouleau
  57. Centre d'Etudes et de Recherches en Psychopathologie, Toulouse University, Toulouse, France.

    • Bernadette Rogé
  58. Department of Computational Biology, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.

    • Kathryn Roeder
  59. Department of Statistics, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.

    • Kathryn Roeder
  60. Autism Research Unit, The Hospital for Sick Children, Toronto, Ontario, Canada.

    • Wendy Roberts
  61. Sanger Institute, Hinxton, UK.

    • Karola Rehnström
    •  & Aarno Palotie
  62. National Childrens Research Centre, Our Lady's Hospital Crumlin, Dublin, Ireland.

    • Regina Regan
    •  & Tiago Magalhaes
  63. Academic Centre on Rare Diseases, University College Dublin, Dublin, Ireland.

    • Regina Regan
    • , Tiago Magalhaes
    • , Andrew Green
    • , Sean Ennis
    • , Judith Conroy
    •  & Jillian Casey
  64. Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina, USA.

    • Joseph Piven
  65. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Dalila Pinto
    • , Arthur P Goldberg
    •  & Joseph D Buxbaum
  66. The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Dalila Pinto
    • , Alexander Kolevzon
    •  & Joseph D Buxbaum
  67. The Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Dalila Pinto
    •  & Arthur P Goldberg
  68. Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Dalila Pinto
    • , Alexander Kolevzon
    •  & Joseph D Buxbaum
  69. The John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA.

    • Margaret A Pericak-Vance
    • , John Gilbert
    •  & Michael L Cuccaro
  70. Institute of Mental Health and Medical Faculty, University of Belgrade, Belgrade, Serbia.

    • Milica Pejovic-Milovancevic
  71. Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark.

    • Marianne G Pedersen
    •  & Carsten B Pedersen
  72. Dalla Lana School of Public Health, Toronto, Ontario, Canada.

    • Andrew D Paterson
  73. Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.

    • Jeremy R Parr
    •  & Ann S Le Couteur
  74. Institue of Health and Science, Newcastle University, Newcastle upon Tyne, UK.

    • Jeremy R Parr
    •  & Ann S Le Couteur
  75. Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, UK.

    • Alistair T Pagnamenta
    •  & Anthony P Monaco
  76. Unidade de Neurodesenvolvimento e Autismo do Serviço do Centro de Desenvolvimento da Criança and Centro de Investigação e Formação Clinica, Pediatric Hospital, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

    • Guiomar Oliveira
    • , Susana Mouga
    • , Frederico Duque
    • , Cátia Café
    •  & Joana Almeida
  77. University Clinic of Pediatrics and Institute for Biomedical Imaging and Life Science, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.

    • Guiomar Oliveira
    • , Susana Mouga
    •  & Frederico Duque
  78. Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA.

    • John I Nurnberger
  79. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.

    • John I Nurnberger
    •  & Patrícia B S Celestino-Soper
  80. Program in Medical Neuroscience, Indiana University School of Medicine, Indianapolis, Indiana, USA.

    • John I Nurnberger
  81. Programs on Neurogenetics, Yale University School of Medicine, New Haven, Connecticut, USA.

    • Michael T Murtha
    •  & A Gulhan Ercan-Sencicek
  82. Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island, USA.

    • Eric M Morrow
    •  & Daniel Moreno De Luca
  83. Tufts University, Boston, Massachusetts, USA.

    • Anthony P Monaco
  84. Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.

    • Alison Merikangas
    • , Louise Gallagher
    • , Sean Brennan
    • , Nadia Bolshakova
    •  & Michael Gill
  85. Department of Psychiatry, University of Utah, Salt Lake City, Utah, USA.

    • William M McMahon
    •  & Hilary Coon
  86. Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.

    • Susan G McGrew
  87. Department of Biomedicine–Human Genetics, Aarhus University, Aarhus, Denmark.

    • Manuel Mattheisen
  88. Department of Child, Adolescent Psychiatry and Medical-Social Rehabilitation, Ukrainian Research Institute of Social Forensic Psychiatry and Drug Abuse, Kyiv, Ukraine.

    • Igor Martsenkovsky
  89. Department of Pediatrics and Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.

    • Donna M Martin
  90. Yale Center for Genomic Analysis, Yale University School of Medicine, New Haven, Connecticut, USA.

    • Shrikant M Mane
  91. Department of Child and Adolescent Psychiatry, National University Hospital, Reykjavik, Iceland.

    • Pall Magnusson
  92. Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.

    • Elena Maestrini
    •  & Elena Bacchelli
  93. Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.

    • Jennifer K Lowe
    •  & Daniel H Geschwind
  94. Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

    • Jennifer K Lowe
    •  & Daniel H Geschwind
  95. Center for Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

    • Jennifer K Lowe
    •  & Daniel H Geschwind
  96. Department of Psychiatry, Weill Cornell Medical College, Cornell University, New York, New York, USA.

    • Catherine Lord
  97. Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

    • Pat Levitt
  98. Autism & Developmental Medicine Institute, Geisinger Health System, Danville, Pennsylvania, USA.

    • Christa Lese Martin
  99. Geisinger Health System, Danville, Pennsylvania, USA.

    • David H Ledbetter
  100. FondaMental Foundation, Créteil, France.

    • Marion Leboyer
    • , Richard Delorme
    •  & Thomas Bourgeron
  101. INSERM U955, Paris, France.

    • Marion Leboyer
  102. Faculté de Médecine, Université Paris Est, Créteil, France.

    • Marion Leboyer
  103. Department of Psychiatry, Henri Mondor–Albert Chenevier Hospital, Assistance Publique–Hôpitaux de Paris, Créteil, France.

    • Marion Leboyer
  104. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

    • Christine Ladd-Acosta
  105. Division of Molecular Genome Analysis and Working Group Cancer Genome Research, Deutsches Krebsforschungszentrum, Heidelberg, Germany.

    • Sabine M Klauck
  106. Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA.

    • Suma Jacob
    • , Stephen J Guter
    •  & Edwin H Cook
  107. Institute of Translational Neuroscience and Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota, USA.

    • Suma Jacob
  108. Department of Public Health Sciences, School of Medicine, University of California, Davis, Davis, California, USA.

    • Irva Hertz-Picciotto
  109. The MIND Institute, School of Medicine, University of California, Davis, Davis, California, USA.

    • Irva Hertz-Picciotto
    •  & David Amaral
  110. Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA.

    • Jonathan L Haines
    •  & James S Sutcliffe
  111. Manchester Academic Health Sciences Centre, Manchester, UK.

    • Jonathan M Green
  112. Institute of Brain, Behaviour, and Mental Health, University of Manchester, Manchester, UK.

    • Jonathan M Green
  113. Centre for Medical Genetics, Our Lady's Hospital Crumlin, Dublin, Ireland.

    • Andrew Green
    •  & Sean Ennis
  114. Gillberg Neuropsychiatry Centre, University of Gothenburg, Gothenburg, Sweden.

    • Christopher Gillberg
  115. Department of Psychiatry and Institute for Development and Disability, Oregon Health & Science University, Portland, Oregon, USA.

    • Eric Fombonne
  116. Division of Child and Adolescent Psychiatry, Department of Psychiatry, Miller School of Medicine, University of Miami, Miami, Florida, USA.

    • Susan E Folstein
  117. Disciplines of Genetics and Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.

    • Bridget Fernandez
  118. Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

    • M Daniele Fallin
  119. Human Genetics and Cognitive Functions Unit, Institut Pasteur, Paris, France.

    • Richard Delorme
    •  & Thomas Bourgeron
  120. Centre National de la Recherche Scientifique, URA 2182, Institut Pasteur, Paris, France.

    • Richard Delorme
    •  & Thomas Bourgeron
  121. Department of Child and Adolescent Psychiatry, Robert Debré Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France.

    • Richard Delorme
  122. Duke Center for Autism and Brain Developments, Duke University School of Medicine, Durham, North Carolina, USA.

    • Geraldine Dawson
  123. Duke Institute for Brain Sciences, Duke University School of Medicine, Durham, North Carolina, USA.

    • Geraldine Dawson
  124. Temple Street Children's University Hospital, Dublin, Ireland.

    • Judith Conroy
    •  & Jillian Casey
  125. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.

    • Patrícia B S Celestino-Soper
    •  & Arthur L Beaudet
  126. Department of Psychiatry, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.

    • Rita M Cantor
  127. Department of Human Genetics, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.

    • Rita M Cantor
    •  & Daniel H Geschwind
  128. University Paris Diderot, Sorbonne Paris Cité, Paris, France.

    • Thomas Bourgeron
  129. Institute of Psychiatry, Kings College London, London, UK.

    • Patrick F Bolton
  130. South London and Maudsley Biomedical Research Centre for Mental Health, London, UK.

    • Patrick F Bolton
  131. Department of Women's and Children's Health, Center of Neurodevelopmental Disorders, Karolinska Institutet, Stockholm, Sweden.

    • Sven Bölte
  132. Child and Adolescent Psychiatry, Center for Psychiatry Research, Stockholm County Council, Stockholm, Sweden.

    • Sven Bölte
  133. INSERM U1130, Paris, France.

    • Catalina Betancur
  134. CNRS UMR 8246, Paris, France.

    • Catalina Betancur
  135. Sorbonne Universités, UPMC Université Paris 6, Neuroscience Paris Seine, Paris, France.

    • Catalina Betancur
  136. Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA.

    • Raphael Bernier
  137. Stella Maris Institute for Child and Adolescent Neuropsychiatr, Pisa, Italy.

    • Agatino Battaglia
  138. Paediatric Neurodisability, King's Health Partners, Kings College London, London, UK.

    • Gillian Baird
  139. Mental Health and Addictions Research Unit, University of British Colombia, Vancouver, British Columbia, Canada.

    • Anthony J Bailey
  140. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

    • Joel S Bader
    • , Aravinda Chakravarti
    •  & Dan E Arking
  141. Bloorview Research Institute, University of Toronto, Toronto, Ontario, Canada.

    • Evdokia Anagnostou
  142. Department of Psychiatry, School of Medicine, University of California, Davis, Davis, California, USA.

    • David Amaral
  143. Department of Behavioural Sciences, School of Medicine, University of California, Davis, Davis, California, USA.

    • David Amaral
  144. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Joseph D Buxbaum
  145. The Center for Applied Genomics and Division of Human Genetics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.

    • Hakon Hakonarson
  146. Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Hakon Hakonarson
  147. Department of Psychiatry, Stanford University, Stanford, California, USA.

    • Joachim Hallmayer
  148. Maine Medical Center Research Institute, Portland, Maine, USA.

    • Susan Santangelo
  149. Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, USA.

    • James S Sutcliffe

Consortia

  1. iPSYCH-Broad Autism Group

    A list of members and affiliations appears at the end of the paper.

  2. Psychiatric Genomics Consortium Autism Group

    A list of members and affiliations appears at the end of the paper.

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Contributions

D.J.W., E.M.W., S.R., R.K.W., J.A.K., J.G., K.E.S., J.I.G., A.O., J.B.-G., T.W., D.M.H., R.A., and S.J.S. generated data and/or conducted analyses. E.B.R., M.J.D., D.J.W., S.B., and G.D.S. designed the experiment and tools. D.S., B.D., and J.T. aided in interpretation of the data. E.B.R., M.J.D., P.B.M., and A.D.B. supervised the research. E.B.R., D.J.W., and E.M.W. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Elise B Robinson.

Integrated supplementary information

Supplementary information

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    Supplementary Text and Figures

    Supplementary Figures 1–12, Supplementary Tables 1–22 and Supplementary Note

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/ng.3863

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