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Identification of common genetic risk variants for autism spectrum disorder

Nature Geneticsvolume 51pages431444 (2019) | Download Citation

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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.

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Data availability

The summary statistics are available for download the iPSYCH and at the PGC download sites (see URLs). For access to genotype data from the PGC samples and the iPSYCH sample, researchers should contact the lead principal investigators M.J.D. and A.D.B. for PGC-ASD and iPSYCH-ASD, respectively.

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Acknowledgements

The iPSYCH project is funded by the Lundbeck Foundation (R102-A9118 and R155-2014-1724) and the universities and university hospitals of Aarhus and Copenhagen. Genotyping of iPSYCH and PGC samples was supported by grants from the Lundbeck Foundation, the Stanley Foundation, the Simons Foundation (SFARI 311789 to M.J.D.), and NIMH (5U01MH094432-02 to M.J.D.). The Danish National Biobank resource was supported by the Novo Nordisk Foundation. Data handling and analysis on the GenomeDK HPC facility was supported by NIMH (1U01MH109514-01 to M.C.O.D and A.D.B.). High-performance computer capacity for handling and statistical analysis of iPSYCH data on the GenomeDK HPC facility was provided by the Centre for Integrative Sequencing, iSEQ, Aarhus University, Denmark (grant to A.D.B.). S.D.R. and J.D.B. were supported by NIH grants MH097849 (to J.D.B.) and MH111661 (to J.D.B.), and by the Seaver Foundation (to S.D.R. and J.D.B.). J. Martine was supported by the Wellcome Trust (grant 106047). O.A.A. received funding from the Research Council of Norway (213694, 223273, 248980, and 248778), Stiftelsen KG Jebsen, and South-East Norway Health Authority. We thank the research participants and employees of 23andMe for making this work possible.

Author information

Author notes

  1. A list of members and affiliations appears in the Supplementary Note.

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

Affiliations

  1. The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark

    • Jakob Grove
    • , Thomas D. Als
    • , Manuel Mattheisen
    • , Jonatan Pallesen
    • , Esben Agerbo
    • , Jonas Bybjerg-Grauholm
    • , Marie Bækvad-Hansen
    • , Jane H. Christensen
    • , Ditte Demontis
    • , Christine S. Hansen
    • , Mads Engel Hauberg
    • , Mads V. Hollegaard
    • , Mette Nyegaard
    • , Carsten Bøcker Pedersen
    • , Marianne Giørtz Pedersen
    • , Jesper Buchhave Poulsen
    • , Per Qvist
    • , Henriette N. Buttenschøn
    • , Wesley Thompson
    • , Yunpeng Wang
    • , Shantel Marie Weinsheimer
    • , Merete Nordentoft
    • , David M. Hougaard
    • , Thomas Werge
    • , Ole Mors
    • , Preben Bo Mortensen
    •  & Anders D. Børglum
  2. Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark

    • Jakob Grove
    • , Thomas D. Als
    • , Manuel Mattheisen
    • , Jonatan Pallesen
    • , Jane H. Christensen
    • , Ditte Demontis
    • , Mads Engel Hauberg
    • , Mette Nyegaard
    • , Per Qvist
    • , Henriette N. Buttenschøn
    • , Preben Bo Mortensen
    •  & Anders D. Børglum
  3. Department of Biomedicine–Human Genetics, Aarhus University, Aarhus, Denmark

    • Jakob Grove
    • , Thomas D. Als
    • , Manuel Mattheisen
    • , Jonatan Pallesen
    • , Jane H. Christensen
    • , Ditte Demontis
    • , Mads Engel Hauberg
    • , Mette Nyegaard
    • , Per Qvist
    •  & Anders D. Børglum
  4. Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark

    • Jakob Grove
  5. Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    • Stephan Ripke
    • , Raymond K. Walters
    • , Claire Churchhouse
    • , Jacqueline I. Goldstein
    • , Daniel P. Howrigan
    • , Hailiang Huang
    • , Alicia R. Martin
    • , Duncan S. Palmer
    • , Aarno Palotie
    • , Timothy dPoterba
    • , Elise B. Robinson
    • , F. Kyle Satterstrom
    • , Patrick Turley
    • , Benjamin M. Neale
    •  & Mark J. Daly
  6. Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA

    • Stephan Ripke
    • , Raymond K. Walters
    • , Rich Belliveau
    • , Felecia Cerrato
    • , Kimberly Chambert
    • , Claire Churchhouse
    • , Ashley L. Dumont
    • , Jacqueline I. Goldstein
    • , Daniel P. Howrigan
    • , Hailiang Huang
    • , Julian Maller
    • , Joanna Martin
    • , Alicia R. Martin
    • , Jennifer L. Moran
    • , Duncan S. Palmer
    • , Aarno Palotie
    • , Timothy dPoterba
    • , Elise B. Robinson
    • , F. Kyle Satterstrom
    • , Christine R. Stevens
    • , Patrick Turley
    • , Erin C. Dunn
    • , Jordan W. Smoller
    • , Benjamin M. Neale
    •  & Mark J. Daly
  7. Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin, Berlin, Germany

    • Stephan Ripke
    •  & Swapnil Awashti
  8. Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany

    • Manuel Mattheisen
  9. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

    • Manuel Mattheisen
  10. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    • Hyejung Won
    •  & Patrick F. Sullivan
  11. UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    • Hyejung Won
  12. National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark

    • Esben Agerbo
    • , Carsten Bøcker Pedersen
    • , Marianne Giørtz Pedersen
    •  & Preben Bo Mortensen
  13. Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark

    • Esben Agerbo
    • , Carsten Bøcker Pedersen
    • , Marianne Giørtz Pedersen
    •  & Preben Bo Mortensen
  14. NORMENT-KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway

    • Ole A. Andreassen
    • , Francesco Bettella
    • , Srdjan Djurovic
    • , Sigrun Hope
    • , Terje Nærland
    • , Wesley Thompson
    •  & Yunpeng Wang
  15. Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway

    • Ole A. Andreassen
    • , Francesco Bettella
    • , Wesley Thompson
    •  & Yunpeng Wang
  16. MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK

    • Richard Anney
    • , Joanna Martin
    • , Michael J. Owen
    •  & Michael C. O’Donovan
  17. Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    • Joseph D. Buxbaum
    • , Silvia De Rubeis
    • , Abraham Reichenberg
    • , Jennifer Reichert
    • , Sven Sandin
    •  & Xinyi Xu
  18. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    • Joseph D. Buxbaum
    • , Silvia De Rubeis
    • , Abraham Reichenberg
    • , Jennifer Reichert
    • , Panos Roussos
    • , Sven Sandin
    •  & Xinyi Xu
  19. Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    • Joseph D. Buxbaum
    •  & Abraham Reichenberg
  20. Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    • Joseph D. Buxbaum
  21. Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark

    • Jonas Bybjerg-Grauholm
    • , Marie Bækvad-Hansen
    • , Christine S. Hansen
    • , Mads V. Hollegaard
    • , Jesper Buchhave Poulsen
    •  & David M. Hougaard
  22. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA

    • Claire Churchhouse
    • , Jacqueline I. Goldstein
    • , Alicia R. Martin
    • , Aarno Palotie
    • , Timothy dPoterba
    • , F. Kyle Satterstrom
    • , Tõnu Esko
    • , Benjamin M. Neale
    •  & Mark J. Daly
  23. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    • Karin Dellenvall
    • , Christina M. Hultman
    • , Joanna Martin
    • , Sven Sandin
    • , Patrick F. Sullivan
    • , Julien Bryois
    • , Erik Pettersson
    • , Alexander Viktorin
    • , Patrik K. Magnusson
    •  & Nancy L. Pedersen
  24. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    • Bernie Devlin
    •  & Lambertus Klei
  25. Department of Medical Genetics, Oslo University Hospital, Oslo, Norway

    • Srdjan Djurovic
  26. Institute of Biological Psychiatry, MHC SctHans, Mental Health Services, Copenhagen, Denmark

    • Christine S. Hansen
    •  & Thomas Werge
  27. Department of Neurohabilitation, Oslo University Hospital, Oslo, Norway

    • Sigrun Hope
  28. Genomics plc, Oxford, UK

    • Julian Maller
  29. Vertex Pharmaceuticals, Abingdon, UK

    • Julian Maller
  30. NevSom, Department of Rare Disorders and Disabilities, , Oslo University Hospital, Oslo, Norway

    • Terje Nærland
  31. Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland

    • Aarno Palotie
    •  & Mark J. Daly
  32. Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands

    • Beate St Pourcain
  33. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK

    • Beate St Pourcain
    •  & George Davey Smith
  34. Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands

    • Beate St Pourcain
  35. Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK

    • Karola Rehnström
  36. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    • Elise B. Robinson
    •  & Hilary K. Finucane
  37. Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA

    • Kathryn Roeder
  38. Department of Statistics and Data Science, Carnegie Mellon University, Pittsburgh, PA, USA

    • Kathryn Roeder
  39. Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    • Panos Roussos
  40. Friedman Brain Institute, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    • Panos Roussos
  41. Mental Illness Research Education and Clinical Center (MIRECC), James J. Peters VA Medical Center, Bronx, NY, USA

    • Panos Roussos
  42. The State Diagnostic and Counselling Centre, Kópavogur, Iceland

    • Evald Saemundsen
  43. Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK

    • George Davey Smith
  44. deCODE genetics/Amgen, Reykjavík, Iceland

    • Hreinn Stefansson
    • , Stacy Steinberg
    • , G. Bragi Walters
    •  & Kari Stefansson
  45. Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    • Patrick F. Sullivan
  46. Faculty of Medicine, University of Iceland, Reykjavik, Iceland

    • G. Bragi Walters
    •  & Kari Stefansson
  47. Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA

    • Daniel H. Geschwind
  48. Center for Autism Research and Treatment and Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA

    • Daniel H. Geschwind
  49. Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA

    • Daniel H. Geschwind
  50. Mental Health Services in the Capital Region of Denmark, Mental Health Center Copenhagen, University of Copenhagen, Copenhagen, Denmark

    • Merete Nordentoft
  51. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

    • Thomas Werge
  52. Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark

    • Ole Mors
  53. Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia

    • Naomi R. Wray
    • , Maciej Trzaskowski
    • , Enda M. Byrne
    • , Grant W. Montgomery
    • , Peter M. Visscher
    • , Yang Wu
    •  & Futao Zhang
  54. Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia

    • Naomi R. Wray
    • , Robert M. Maier
    • , Divya Mehta
    • , Peter M. Visscher
    •  & Jian Yang
  55. Department of Biological Psychology & EMGO+ Institute for Health and Care Research, Vrije Universiteit, Amsterdam, Amsterdam, the Netherlands

    • Abdel Abdellaoui
    • , Conor V. Dolan
    • , Jouke-Jan Hottenga
    • , Hamdi Mbarek
    • , Christel M. Middeldorp
    • , Michel G. Nivard
    • , Gonneke Willemsen
    • , Dorret I. Boomsma
    •  & E. J. C. de Geus
  56. Division of Psychiatry, University of Edinburgh, Edinburgh, UK

    • Mark J. Adams
    • , Douglas H. R. Blackwood
    • , Toni-Kim Clarke
    • , Lynsey S. Hall
    •  & Andrew M. McIntosh
  57. Discipline of Psychiatry, University of Adelaide, Adelaide, South Australia, Australia

    • Tracy M. Air
    •  & Bernhard T. Baune
  58. Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany

    • Till F. M. Andlauer
    • , Elisabeth B. Binder
    •  & Bertram Müller-Myhsok
  59. Munich Cluster for Systems Neurology (SyNergy), Munich, Germany

    • Till F. M. Andlauer
    •  & Bertram Müller-Myhsok
  60. Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA

    • Silviu-Alin Bacanu
    • , Tim B. Bigdeli
    • , Roseann E. Peterson
    • , Brien P. Riley
    •  & Kenneth S. Kendler
  61. Department of Psychiatry, Vrije Universiteit Medical Center and GGZ inGeest, Amsterdam, the Netherlands

    • Aartjan T. F. Beekman
    • , Rick Jansen
    • , Rick Jansen
    • , Yuri Milaneschi
    • , Yuri Milaneschi
    • , Wouter J. Peyrot
    • , Johannes H. Smit
    •  & Brenda W. J. H. Penninx
  62. Virginia Institute for Psychiatric and Behavior Genetics, Richmond, VA, USA

    • Tim B. Bigdeli
  63. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA

    • Elisabeth B. Binder
  64. Department of Clinical Medicine, Translational Neuropsychiatry Unit, Aarhus University, Aarhus, Denmark

    • Henriette N. Buttenschøn
  65. Human Genetics, Wellcome Trust Sanger Institute, Cambridge, UK

    • Na Cai
  66. Statistical genomics and systems genetics, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK

    • Na Cai
  67. Department of Psychiatry, University Hospital of Lausanne, Prilly, Switzerland

    • Enrique Castelao
    • , Giorgio Pistis
    •  & Martin Preisig
  68. MRC Social Genetic and Developmental Psychiatry Centre, King’s College London, London, UK

    • Jonathan R. I. Coleman
    • , Thalia C. Eley
    • , Héléna A. Gaspar
    • , Peter McGuffin
    • , Niamh Mullins
    • , Paul F. O’Reilly
    • , Margarita Rivera
    • , Cathryn M. Lewis
    •  & Gerome Breen
  69. Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

    • Lucía Colodro-Conde
    • , Eske M. Derks
    • , Scott D. Gordon
    • , Penelope A. Lind
    • , Sarah E. Medland
    • , Jodie N. Painter
    •  & Nicholas G. Martin
  70. Centre for Advanced Imaging, University of Queensland, Saint Lucia, Queensland, Australia

    • Baptiste Couvy-Duchesne
  71. Queensland Brain Institute, University of Queensland, Saint Lucia, Queensland, Australia

    • Baptiste Couvy-Duchesne
  72. Psychological Medicine, Cardiff University, Cardiff, UK

    • Nick Craddock
  73. Center for Genomic and Computational Biology, Duke University, Durham, NC, USA

    • Gregory E. Crawford
  74. Department of Pediatrics, Division of Medical Genetics, Duke University, Durham, NC, USA

    • Gregory E. Crawford
  75. Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK

    • Gail Davies
    • , Ian J. Deary
    •  & Andrew M. McIntosh
  76. Institute of Human Genetics, University of Bonn, Bonn, Germany

    • Franziska Degenhardt
    • , Andreas J. Forstner
    • , Stefan Herms
    • , Per Hoffmann
    • , Sven Cichon
    •  & Markus M. Nöthen
  77. Life&Brain Center, Department of Genomics, University of Bonn, Bonn, Germany

    • Franziska Degenhardt
    • , Andreas J. Forstner
    • , Stefan Herms
    • , Per Hoffmann
    •  & Markus M. Nöthen
  78. Epidemiology, Erasmus MC, Rotterdam, the Netherlands

    • Nese Direk
    • , Saira Saeed Mirza
    •  & Henning Tiemeier
  79. Psychiatry, Dokuz Eylul University School Of Medicine, Izmir, Turkey

    • Nese Direk
  80. Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA

    • Erin C. Dunn
    • , Roy H. Perlis
    •  & Jordan W. Smoller
  81. Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Massachusetts General Hospital, Boston, MA, USA

    • Erin C. Dunn
    •  & Jordan W. Smoller
  82. Neuroscience and Mental Health, Cardiff University, Cardiff, UK

    • Valentina Escott-Price
  83. Bioinformatics, University of British Columbia, Vancouver, British Columbia, Canada

    • Farnush Farhadi Hassan Kiadeh
  84. Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA, USA

    • Hilary K. Finucane
  85. Department of Psychiatry (UPK), University of Basel, Basel, Switzerland

    • Andreas J. Forstner
  86. Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland

    • Andreas J. Forstner
    • , Stefan Herms
    • , Per Hoffmann
    •  & Sven Cichon
  87. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty, Mannheim, Heidelberg University, Mannheim, Baden-Württemberg, Germany

    • Josef Frank
    • , Fabian Streit
    • , Jana Strohmaier
    • , Jens Treutlein
    • , Stephanie H. Witt
    • , Marcella Rietschel
    •  & Thomas G. Schulze
  88. Department of Psychiatry, Trinity College Dublin, Dublin, Ireland

    • Michael Gill
  89. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA

    • Fernando S. Goes
    • , Dean F. MacKinnon
    • , Francis M. Mondimore
    • , J. Raymond DePaulo
    •  & Thomas G. Schulze
  90. Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK

    • Lynsey S. Hall
  91. Danish Headache Centre, Department of Neurology, Rigshospitalet, Glostrup, Denmark

    • Thomas F. Hansen
  92. Institute of Biological Psychiatry, Mental Health Center SctHans, Mental Health Services Capital Region of Denmark, Copenhagen, Denmark

    • Thomas F. Hansen
    • , Wesley Thompson
    • , Yunpeng Wang
    •  & Shantel Marie Weinsheimer
  93. iPSYCH, Lundbeck Foundation Initiative for Psychiatric Research, Copenhagen, Denmark

    • Thomas F. Hansen
  94. Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia

    • Ian B. Hickie
  95. Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine and Ernst Moritz Arndt University Greifswald, Greifswald, Mecklenburg-Vorpommern, Germany

    • Georg Homuth
  96. Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, FHoffmann-La Roche Ltd, Basel, Switzerland

    • Carsten Horn
  97. Max Planck Institute of Psychiatry, Munich, Germany

    • Marcus Ising
    • , Stefan Kloiber
    •  & Susanne Lucae
  98. Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA

    • Eric Jorgenson
    • , Ling Shen
    •  & Catherine Schaefer
  99. Psychiatry & The Behavioral Sciences, University of Southern California, Los Angeles, CA, USA

    • James A. Knowles
  100. Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA

    • Isaac S. Kohane
  101. Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA

    • Isaac S. Kohane
  102. Informatics Program, Boston Children’s Hospital, Boston, MA, USA

    • Isaac S. Kohane
  103. Department of Psychiatry and Psychotherapy, Universitätsmedizin Berlin Campus Charité Mitte, Berlin, Germany

    • Julia Kraft
    •  & Vassily Trubetskoy
  104. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

    • Warren W. Kretzschmar
    •  & Yihan Li
  105. Department of Endocrinology at Herlev University Hospital, University of Copenhagen, Copenhagen, Denmark

    • Jesper Krogh
  106. Institute of Social and Preventive Medicine (IUMSP), University Hospital of Lausanne, Lausanne, Switzerland

    • Zoltán Kutalik
  107. Swiss Institute of Bioinformatics, Lausanne, Switzerland

    • Zoltán Kutalik
  108. Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK

    • Donald J. MacIntyre
  109. Mental Health, NHS 24, Glasgow, UK

    • Donald J. MacIntyre
  110. Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany

    • Wolfgang Maier
  111. Statistics, University of Oxford, Oxford, UK

    • Jonathan Marchini
  112. Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA

    • Patrick McGrath
    •  & Myrna M. Weissman
  113. School of Psychology and Counseling, Queensland University of Technology, Brisbane, Queensland, Australia

    • Divya Mehta
  114. Child and Youth Mental Health Service, Children’s Health Queensland Hospital and Health Service, South Brisbane, Queensland, Australia

    • Christel M. Middeldorp
  115. Child Health Research Centre, University of Queensland, Brisbane, Queensland, Australia

    • Christel M. Middeldorp
  116. Estonian Genome Center, University of Tartu, Tartu, Estonia

    • Evelin Mihailov
    • , Lili Milani
    • , Tõnu Esko
    •  & Andres Metspalu
  117. Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada

    • Sara Mostafavi
  118. Statistics, University of British Columbia, Vancouver, British Columbia, Canada

    • Sara Mostafavi
    •  & Bernard Ng
  119. DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, University Medicine, University Medicine Greifswald, Greifswald, Germany

    • Matthias Nauck
  120. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine, Greifswald, Germany

    • Matthias Nauck
  121. Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia

    • Dale R. Nyholt
  122. Humus, Reykjavik, Iceland

    • Hogni Oskarsson
  123. Virginia Institute for Psychiatric & Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA

    • Roseann E. Peterson
    •  & Bradley T. Webb
  124. Clinical Genetics, Vrije Universiteit Medical Center, Amsterdam, the Netherlands

    • Danielle Posthuma
  125. Complex Trait Genetics, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands

    • Danielle Posthuma
  126. Solid Biosciences, Boston, MA, USA

    • Jorge A. Quiroz
  127. Department of Psychiatry, Washington University in Saint Louis School of Medicine, Saint Louis, MO, USA

    • John P. Rice
    • , Andrew C. Heath
    •  & Pamela A. F. Madden
  128. Department of Biochemistry and Molecular Biology II, Institute of Neurosciences, Center for Biomedical Research, University of Granada, Granada, Spain

    • Margarita Rivera
  129. Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

    • Robert Schoevers
  130. Department of Psychiatry and Psychotherapy, Medical Center of the University of Munich, Campus Innenstadt, Munich, Germany

    • Eva C. Schulte
  131. Institute of Psychiatric Phenomics and Genomics (IPPG), Medical Center of the University of Munich, Campus Innenstadt, Munich, Germany

    • Eva C. Schulte
    •  & Thomas G. Schulze
  132. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

    • Jianxin Shi
  133. Behavioral Health Services, Kaiser Permanente Washington, Seattle, WA, USA

    • Stanley I. Shyn
  134. Faculty of Medicine, Department of Psychiatry, University of Iceland, Reykjavik, Iceland

    • Engilbert Sigurdsson
  135. School of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia

    • Grant C. B. Sinnamon
  136. Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK

    • Daniel J. Smith
  137. College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK

    • Katherine E. Tansey
  138. Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany

    • Henning Teismann
    • , Jürgen Wellmann
    •  & Klaus Berger
  139. Institute for Community Medicine, University Medicine, Greifswald, Germany

    • Alexander Teumer
    •  & Henry Völzke
  140. Department of Psychiatry, University of California, San Diego, San Diego, CA, USA

    • Wesley Thompson
  141. Medical Genetics Section, CGEM, IGMM, University of Edinburgh, Edinburgh, UK

    • Pippa A. Thomson
    •  & David J. Porteous
  142. deCODE Genetics/Amgen, Reykjavik, Iceland

    • Thorgeir E. Thorgeirsson
  143. Clinical Neurosciences, University of Cambridge, Cambridge, UK

    • Matthew Traylor
  144. Internal Medicine, Erasmus MC, Rotterdam, the Netherlands

    • André G. Uitterlinden
  145. Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases Discovery & Translational Medicine Area, Roche Innovation Center Basel, FHoffmann-La Roche Ltd, Basel, Switzerland

    • Daniel Umbricht
  146. Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany

    • Sandra Van der Auwera
    •  & Hans J. Grabe
  147. Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands

    • Albert M. van Hemert
  148. Computational Sciences Center of Emphasis, Pfizer Global Research and Development, Cambridge, MA, USA

    • Hualin S. Xi
  149. Institute for Molecular Bioscience, Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia

    • Jian Yang
  150. Department of Psychiatry, University of Münster, Münster, Germany

    • Volker Arolt
    •  & Udo Dannlowski
  151. Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland

    • Sven Cichon
  152. Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany

    • Sven Cichon
  153. Amsterdam Public Health Institute, Vrije Universiteit Medical Center, Amsterdam, the Netherlands

    • E. J. C. de Geus
  154. Centre for Integrative Biology, Università degli Studi di Trento, Trento, Trentino-Alto Adige, Italy

    • Enrico Domenici
  155. Department of Psychiatry and Psychotherapy, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany

    • Katharina Domschke
  156. Psychiatry, Kaiser Permanente Northern California, San Francisco, CA, USA

    • Steven P. Hamilton
  157. Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK

    • Caroline Hayward
  158. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

    • Stefan Kloiber
  159. Centre for Addiction and Mental Health, Toronto, Ontario, Canada

    • Stefan Kloiber
  160. Division of Psychiatry, University College London, London, UK

    • Glyn Lewis
  161. Neuroscience Therapeutic Area, Janssen Research and Development, LLC, Titusville, NJ, USA

    • Qingqin S. Li
  162. Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia

    • Andres Metspalu
  163. University of Liverpool, Liverpool, UK

    • Bertram Müller-Myhsok
  164. Human Genetics and Computational Biomedicine, Pfizer Global Research and Development, Groton, CT, USA

    • Sara A. Paciga
  165. Psychiatry, Harvard Medical School, Boston, MA, USA

    • Roy H. Perlis
  166. Psychiatry, University of Iowa, Iowa City, IA, USA

    • James B. Potash
  167. Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany

    • Thomas G. Schulze
  168. Human Genetics Branch, NIMH Division of Intramural Research Programs, Bethesda, MD, USA

    • Thomas G. Schulze
  169. Child and Adolescent Psychiatry, Erasmus MC, Rotterdam, the Netherlands

    • Henning Tiemeier
  170. Psychiatry, Erasmus MC, Rotterdam, the Netherlands

    • Henning Tiemeier
  171. Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada

    • Rudolf Uher
  172. Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA

    • Myrna M. Weissman
  173. Department of Medical & Molecular Genetics, King’s College London, London, UK

    • Cathryn M. Lewis
  174. Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, USA

    • Douglas F. Levinson
  175. NIHR BRC for Mental Health, King’s College London, London, UK

    • Gerome Breen
  176. 23andMe, Inc., Mountain View, CA, USA

    • 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

Authors

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Consortia

  1. Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium

    1. BUPGEN

      1. Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

      1. 23andMe Research Team

      Contributions

      Analysis: J.G., S.R., T.D.A., M.M., R.K.W., H.W., J.P., S.A., F.B., J.H.C., C.C., K.D., S.D.R., B.D., S.D., M.E.H., S.H., D.P.H., H.H., L.K., J. Maller, J. Martin, A.R.M., M. Nyegaard, T.N., D.S.P., T.P., B.S.P., P.Q., J.R., E.B.R., K. Roeder, P.R., S. Sandin, F.K.S., S. Steinberg, P.F.S., P.T., G.B.W., X.X., D.H.G., B.M.N., M.J.D., A.D.B. J.G., B.M.N., M.J.D., and A.D.B. supervised and coordinated the analyses. Sample and/or data provider and processing: J.G., S.R., M.M., R.K.W., E.A., O.A.A., R.A., R.B., J.D.B., J.B.-G., M.B.-H., F.C., K.C., D.D., A.L.D., J.I.G., C.S.H., M.V.H., C.M.H., J.L.M., A.P., C.B.P., M.G.P., J.B.P., K. Rehnström, A.R., E.S., G.D.S., H.S., C.R.S., Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium, BUPGEN, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, 23andMe Research Team, K.S., D.M.H., O.M., P.B.M., B.M.N., M.J.D., and A.D.B. Core PI group: K.S., D.H.G., M. Nordentoft, D.M.H., T.W., O.M., P.B.M., B.M.N., M.J.D., and A.D.B. Core writing group: J.G., M.J.D., and A.D.B. Direction of study: M.J.D. and A.D.B.

      Competing interests

      H.S., K.S., S. Steinberg, and G.B.W. are employees of deCODE genetics/Amgen. The 23andMe Research Team members are employed by 23andMe. D.H.G. is a scientific advisor for Ovid Therapeutic, Falcon Computing, and Axial Biotherapeutics. T.W. has acted as scientific advisor and lecturer for H. Lundbeck A/S.

      Corresponding authors

      Correspondence to Mark J. Daly or Anders D. Børglum.

      Supplementary information

      1. Supplementary Text and Figures

        Supplementary Note, Supplementary Tables 1–16 and Supplementary Figures 1–98

      2. Reporting Summary

      About this article

      Publication history

      Received

      Accepted

      Published

      Issue Date

      DOI

      https://doi.org/10.1038/s41588-019-0344-8