Letter | Published:

Common genetic variants influence human subcortical brain structures

Nature volume 520, pages 224229 (09 April 2015) | Download Citation

Abstract

The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

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Acknowledgements

Funding sources for contributing sites and acknowledgments of contributing consortia authors can be found in Supplementary Note 3.

Author information

Author notes

    • Derrek P. Hibar
    • , Jason L. Stein
    • , Miguel E. Renteria
    • , Alejandro Arias-Vasquez
    •  & Sylvane Desrivières

    These authors contributed equally to this work.

    • Nicholas G. Martin
    • , Margaret J. Wright
    • , Gunter Schumann
    • , Barbara Franke
    • , Paul M. Thompson
    •  & Sarah E. Medland

    These authors jointly supervised this work.

Affiliations

  1. Imaging Genetics Center, Institute for Neuroimaging & Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California 90292, USA.

    • Derrek P. Hibar
    • , Jason L. Stein
    • , Neda Jahanshad
    • , Christopher R. K. Ching
    • , Christopher D. Whelan
    •  & Paul M. Thompson
  2. Neurogenetics Program, Department of Neurology, UCLA School of Medicine, Los Angeles, California 90095, USA.

    • Jason L. Stein
  3. QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.

    • Miguel E. Renteria
    • , Gabriel Cuellar-Partida
    • , Lachlan T. Strike
    • , Narelle K. Hansell
    • , Grant W. Montgomery
    • , Nicholas G. Martin
    • , Margaret J. Wright
    •  & Sarah E. Medland
  4. Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands.

    • Alejandro Arias-Vasquez
    • , Janita Bralten
    • , Martine Hoogman
    • , Marieke Klein
    • , Marjolein M. J. van Donkelaar
    • , Marina M. H. Hakobjan
    • , Angelien J. G. A. M. Heister
    • , Remco R. R. Makkinje
    • , Marlies A. M. Naber
    • , Saskia S. L. van der Marel
    • , Kimm J. E. van Hulzen
    • , Jeanette C. Mostert
    • , Han G. Brunner
    • , Hans van Bokhoven
    •  & Barbara Franke
  5. Department of Psychiatry, Radboud university medical center, Nijmegen 6500 HB, The Netherlands.

    • Alejandro Arias-Vasquez
    •  & Barbara Franke
  6. Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen 6500 HB, The Netherlands.

    • Alejandro Arias-Vasquez
    • , Janita Bralten
    • , Jan K. Buitelaar
    •  & Guillén Fernández
  7. Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands.

    • Alejandro Arias-Vasquez
    • , Janita Bralten
    • , Martine Hoogman
    • , Marieke Klein
    • , Marjolein M. J. van Donkelaar
    • , Marcel P. Zwiers
    • , Marina M. H. Hakobjan
    • , Angelien J. G. A. M. Heister
    • , Remco R. R. Makkinje
    • , Marlies A. M. Naber
    • , Saskia S. L. van der Marel
    • , Kimm J. E. van Hulzen
    • , Jeanette C. Mostert
    • , Han G. Brunner
    • , Jan K. Buitelaar
    • , Hans van Bokhoven
    • , Guillén Fernández
    • , Simon E. Fisher
    • , Clyde Francks
    •  & Barbara Franke
  8. MRC-SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK.

    • Sylvane Desrivières
    • , Tianye Jia
    • , Christine Macare
    •  & Gunter Schumann
  9. Laboratory of Human Genetics and Cognitive Functions, Institut Pasteur, Paris 75015, France.

    • Roberto Toro
  10. Centre Nationale de Recherche Scientifique (CNRS) Unité de Recherche Associée (URA) 2182 Genes, Synapses and Cognition, Institut Pasteur, Paris 75015, France.

    • Roberto Toro
  11. Université Paris Diderot, Sorbonne Paris Cité, Paris 75015, France.

    • Roberto Toro
  12. German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald 17487, Germany.

    • Katharina Wittfeld
    •  & Wolfgang Hoffmann
  13. Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany.

    • Katharina Wittfeld
    • , Deborah Janowitz
    •  & Hans J. Grabe
  14. Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands.

    • Lucija Abramovic
    • , Marc M. Bohlken
    • , Marco P. Boks
    • , Kristel R. van Eijk
    • , Wiepke Cahn
    • , René S. Kahn
    • , Neeltje E. M. van Haren
    • , Rachel M. Brouwer
    • , Hilleke E. Hulshoff Pol
    •  & Roel A. Ophoff
  15. Umeå Centre for Functional Brain Imaging (UFBI), Umeå University, Umeå 901 87, Sweden.

    • Micael Andersson
    • , Alireza Salami
    • , Lars G. Nilsson
    •  & Lars Nyberg
  16. Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK.

    • Benjamin S. Aribisala
    • , Natalie A. Royle
    • , Mark E. Bastin
    •  & Joanna M. Wardlaw
  17. Department of Computer Science, Lagos State University, Lagos, Nigeria.

    • Benjamin S. Aribisala
  18. Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK.

    • Benjamin S. Aribisala
    • , Natalie A. Royle
    • , Mark E. Bastin
    •  & Joanna M. Wardlaw
  19. Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia.

    • Nicola J. Armstrong
    • , Karen A. Mather
    • , Amelia A. Assareh
    • , Henry Brodaty
    • , Simone Reppermund
    • , Anbupalam Thalamuthu
    • , Wei Wen
    •  & Perminder S. Sachdev
  20. School of Mathematics and Statistics, University of Sydney, Sydney 2006, Australia.

    • Nicola J. Armstrong
  21. The Hospital for Sick Children, University of Toronto, Toronto M5G 1X8, Canada.

    • Manon Bernard
    • , Jean Shin
    •  & Zdenka Pausova
  22. NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway.

    • Andrew A. Brown
    • , Lavinia Athanasiu
    • , Cecilie B. Hartberg
    • , Unn K. Haukvik
    • , Ingrid Melle
    • , Srdjan Djurovic
    • , Ingrid Agartz
    • , Ole A. Andreassen
    •  & Erik G. Jönsson
  23. NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0424, Norway.

    • Andrew A. Brown
    • , Lars T. Westlye
    • , Lavinia Athanasiu
    • , Ingrid Melle
    • , Thomas Espeseth
    •  & Ole A. Andreassen
  24. Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal H4H 1R3, Canada.

    • M. Mallar Chakravarty
  25. Department of Psychiatry and Biomedical Engineering, McGill University, Montreal H3A 2B4, Canada.

    • M. Mallar Chakravarty
  26. Lieber Institute for Brain Development, Baltimore, Maryland 21205, USA.

    • Qiang Chen
    • , Aaron L. Goldman
    • , Venkata S. Mattay
    •  & Daniel R. Weinberger
  27. Interdepartmental Neuroscience Graduate Program, UCLA School of Medicine, Los Angeles, California 90095, USA.

    • Christopher R. K. Ching
  28. Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands.

    • Anouk den Braber
    • , Iryna O. Fedko
    • , Jouke-Jan Hottenga
    • , Dennis van 't Ent
    • , Dorret I. Boomsma
    •  & Eco J. C. de Geus
  29. NORMENT - KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway.

    • Sudheer Giddaluru
    • , Vidar M. Steen
    •  & Stephanie Le Hellard
  30. Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen 5021, Norway.

    • Sudheer Giddaluru
    • , Vidar M. Steen
    •  & Stephanie Le Hellard
  31. Central Institute of Mental Health, Medical Faculty Mannheim, University Heidelberg, Mannheim 68159, Germany.

    • Oliver Grimm
    • , Marcella Rietschel
    •  & Andreas Meyer-Lindenberg
  32. Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen 6525 XD, The Netherlands.

    • Tulio Guadalupe
    • , Simon E. Fisher
    •  & Clyde Francks
  33. International Max Planck Research School for Language Sciences, Nijmegen 6525 XD, The Netherlands.

    • Tulio Guadalupe
  34. Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, Dresden 01307 Germany.

    • Johanna Hass
    • , Stefan Ehrlich
    •  & Esther Walton
  35. Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland 20892, USA.

    • Girma Woldehawariat
    • , Allison C. Nugent
    • , Xinmin Liu
    • , Francis J. McMahon
    • , Wayne C. Drevets
    •  & Dara M. Cannon
  36. Department of Psychology, Yale University, New Haven, Connecticut 06511, USA.

    • Avram J. Holmes
  37. Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA.

    • Avram J. Holmes
    • , Phil H. Lee
    • , Stefan Ehrlich
    • , Randy L. Buckner
    • , Randy L. Gollub
    • , Joshua L. Roffman
    •  & Jordan W. Smoller
  38. Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

    • Sungeun Kim
    • , Kwangsik Nho
    • , Shannon L. Risacher
    • , Li Shen
    •  & Andrew J. Saykin
  39. Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

    • Sungeun Kim
    • , Kwangsik Nho
    •  & Li Shen
  40. Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

    • Sungeun Kim
    • , Kwangsik Nho
    • , Shannon L. Risacher
    • , Li Shen
    • , Tatiana M. Foroud
    •  & Andrew J. Saykin
  41. Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany.

    • Bernd Kraemer
    • , Maria Keil
    •  & Oliver Gruber
  42. Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02115, USA.

    • Phil H. Lee
    •  & Jordan W. Smoller
  43. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Boston, Massachusetts 02141, USA.

    • Phil H. Lee
    •  & Jordan W. Smoller
  44. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02115, USA.

    • Phil H. Lee
  45. Center for Neurobehavioral Genetics, University of California, Los Angeles, California 90095, USA.

    • Loes M. Olde Loohuis
    •  & Roel A. Ophoff
  46. Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.

    • Michelle Luciano
    • , David C. M. Liewald
    • , Lorna M. Lopez
    • , Natalie A. Royle
    • , Mark E. Bastin
    • , Ian J. Deary
    • , Andrew M. McIntosh
    •  & Joanna M. Wardlaw
  47. Department of Biomedicine, Aarhus University, Aarhus DK-8000, Denmark.

    • Manuel Mattheisen
  48. The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen DK-8000, Denmark.

    • Manuel Mattheisen
  49. Center for integrated Sequencing, iSEQ, Aarhus University, Aarhus DK-8000, Denmark.

    • Manuel Mattheisen
  50. Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam 1081 HL, The Netherlands.

    • Yuri Milaneschi
    • , Lianne Schmaal
    • , Dick J. Veltman
    •  & Brenda W. J. H. Penninx
  51. Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH10 5HF, UK.

    • Martina Papmeyer
    • , Emma Sprooten
    • , Stephen M. Lawrie
    • , Jessika E. Sussmann
    •  & Andrew M. McIntosh
  52. Department of Medical and Molecular Genetics, King’s College London, London SE1 9RT, UK.

    • Adaikalavan Ramasamy
    • , Mina Ryten
    •  & Michael E. Weale
  53. Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK.

    • Adaikalavan Ramasamy
    • , Daniah Trabzuni
    • , J. Raphael Gibbs
    • , Sebastian Guelfi
    • , Dena G. Hernandez
    • , John Hardy
    •  & Mina Ryten
  54. Department of Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria-IDIVAL, Santander 39008, Spain.

    • Roberto Roiz-Santiañez
    •  & Benedicto Crespo-Facorro
  55. Cibersam (Centro Investigación Biomédica en Red Salud Mental), Madrid 28029, Spain.

    • Roberto Roiz-Santiañez
    • , Rocio Perez-Iglesias
    •  & Benedicto Crespo-Facorro
  56. Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 2, Ireland.

    • Emma J. Rose
    • , Margaret Needham
    • , Aiden Corvin
    • , Derek W. Morris
    •  & Gary Donohoe
  57. Center for Translational Research on Adversity, Neurodevelopment and Substance Abuse (C-TRANS), Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland 21045, USA.

    • Emma J. Rose
  58. Aging Research Center, Karolinska Institutet and Stockholm University, 11330 Stockholm, Sweden.

    • Alireza Salami
  59. Max Planck Institute of Psychiatry, Munich 80804, Germany.

    • Philipp G. Sämann
    • , David Hoehn
    • , Benno Pütz
    • , Christiane Wolf
    • , Michael Czisch
    • , Florian Holsboer
    • , Bertram Müller-Myhsok
    •  & Oliver Gruber
  60. Multimodal Imaging Laboratory, Department of Neurosciences, University of California, San Diego, California 92093, USA.

    • Andrew J. Schork
  61. Department of Cognitive Sciences, University of California, San Diego, California 92161, USA.

    • Andrew J. Schork
  62. School of Psychology, University of Queensland, Brisbane 4072, Australia.

    • Lachlan T. Strike
    • , Greig I. de Zubicaray
    •  & Margaret J. Wright
  63. Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia.

    • Lachlan T. Strike
    •  & Katie L. McMahon
  64. Institute for Community Medicine, University Medicine Greifswald, Greifswald D-17475, Germany.

    • Alexander Teumer
    • , Wolfgang Hoffmann
    •  & Henry Völzke
  65. Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

    • Raymond K. Walters
  66. Medical and Population Genetics Program, Broad Institute of Harvard and MIT, Boston, Massachusetts 02142, USA.

    • Raymond K. Walters
  67. Department of Psychology, University of Oslo, Oslo 0373, Norway.

    • Lars T. Westlye
    • , Ivar Reinvang
    •  & Thomas Espeseth
  68. The Oxford Centre for Functional MRI of the Brain, Nuffield Department of Clinical Neurosciences, Oxford University, Oxford OX3 9DU, UK.

    • Anderson M. Winkler
  69. Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511, USA.

    • Anderson M. Winkler
    • , D. Reese McKay
    • , Emma Sprooten
    •  & David C. Glahn
  70. Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal H3A 2B4, Canada.

    • Saud Alhusaini
  71. Molecular and Cellular Therapeutics, The Royal College of Surgeons, Dublin 2, Ireland.

    • Norman Delanty
  72. The Athinoula A.Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.

    • Stefan Ehrlich
    • , Randy L. Gollub
    • , Maritza Ebling
    • , Bruce Fischl
    • , Douglas Greve
    •  & Louis N. Vinke
  73. Department of Psychiatric Research and Development, Diakonhjemmet Hospital, Oslo 0319, Norway.

    • Cecilie B. Hartberg
    •  & Ingrid Agartz
  74. UCL Institute of Neurology, London, United Kingdom and Epilepsy Society, London WC1N 3BG, UK.

    • Dalia Kasperaviciute
    •  & Sanjay M. Sisodiya
  75. Department of Medicine, Imperial College London, London W12 0NN, UK.

    • Dalia Kasperaviciute
  76. Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WC1N 3BG, UK.

    • Mar Matarin
  77. Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut 06106, USA.

    • D. Reese McKay
    • , Emma Sprooten
    •  & David C. Glahn
  78. Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia.

    • Daniah Trabzuni
  79. Texas Biomedical Research Institute, San Antonio, Texas 78245, USA.

    • Laura Almasy
    • , Melanie A. Carless
    • , Joanne E. Curran
    • , Ravi Duggirala
    • , Thomas D. Dyer
    • , Harald H. H. Göring
    • , Jack W. Kent Jr
    •  & John Blangero
  80. University of Texas Health Science Center, San Antonio, Texas 78229, USA.

    • Laura Almasy
    • , Thomas D. Dyer
    • , Peter T. Fox
    •  & John Blangero
  81. National Ageing Research Institute, Royal Melbourne Hospital, Melbourne 3052, Australia.

    • David Ames
  82. Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne 3101, Australia.

    • David Ames
    • , J. Raphael Gibbs
    •  & Dena G. Hernandez
  83. Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA.

    • Sampath Arepalli
    • , Allissa Dillman
    • , Michael A. Nalls
    • , Bryan J. Traynor
    • , Mark R. Cookson
    •  & Andrew Singleton
  84. Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK.

    • Mark E. Bastin
    • , Maria C. Valdés Hernández
    •  & Joanna M. Wardlaw
  85. N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia.

    • Kazima B. Bulayeva
  86. Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel 4055, Switzerland.

    • Sven Cichon
  87. Institute of Human Genetics, University of Bonn, Bonn, D-53127, Germany.

    • Sven Cichon
    • , Thomas W. Mühleisen
    •  & Markus M. Nöthen
  88. Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, D-52425, Germany.

    • Sven Cichon
    •  & Thomas W. Mühleisen
  89. Department of Genomics, Life & Brain Center, University of Bonn, Bonn D-53127, Germany.

    • Sven Cichon
    • , Andreas Heinz
    • , Thomas W. Mühleisen
    •  & Markus M. Nöthen
  90. Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, CCM, Berlin 10117, Germany.

    • Susanne Erk
    • , Sebastian Mohnke
    • , Nina Romanczuk-Seiferth
    • , Henrik Walter
    •  & Andrew J. Saykin
  91. Clinical Research Branch, National Institute on Aging, Baltimore, Maryland 20892, USA.

    • Luigi Ferrucci
  92. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

    • Tatiana M. Foroud
    •  & Rene L. Olvera
  93. South Texas Veterans Health Care System, San Antonio, Texas 78229, USA.

    • Peter T. Fox
  94. Biofunctional Imaging, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.

    • Masaki Fukunaga
  95. Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts 02115, USA.

    • Robert C. Green
  96. Harvard Medical School, Boston, Massachusetts 02115, USA.

    • Robert C. Green
    • , Randy L. Gollub
    •  & Jordan W. Smoller
  97. Department of Psychiatry, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.

    • Catharina A. Hartman
    •  & Pieter J. Hoekstra
  98. Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald 17475, Germany.

    • Katrin Hegenscheid
    •  & Norbert Hosten
  99. Departments of Cognitive and Clinical Neuropsychology, VU University Amsterdam, 1081 BT Amsterdam, The Netherlands

    • Dirk J. Heslenfeld
  100. Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17489, Germany.

    • Georg Homuth
  101. Department of Psychiatry, Fujita Health University School of Medicine, Toyoake 470-1192, Japan.

    • Masashi Ikeda
  102. Radiology, Mayo Clinic, Rochester, Minnesota 55905, USA.

    • Clifford R. Jack Jr
  103. FMRIB Centre, University of Oxford, Oxford OX3 9DU, UK.

    • Mark Jenkinson
    •  & Thomas E. Nichols
  104. NICHD Brain and Tissue Bank for Developmental Disorders, University of Maryland Medical School, Baltimore, Maryland 21201, USA.

    • Robert Johnson
    •  & Ronald H. Zielke
  105. School of Psychology, University of Sussex, Brighton BN1 9QH, UK.

    • Ryota Kanai
  106. Institute of Cognitive Neuroscience, University College London, London WC1N 3AR, UK.

    • Ryota Kanai
  107. Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland, Baltimore, Maryland 21201, USA.

    • Peter Kochunov
  108. Neuroscience Research Australia, Sydney 2031, Australia.

    • John B. Kwok
    •  & Peter R. Schofield
  109. School of Medical Sciences, UNSW, Sydney 2052, Australia.

    • John B. Kwok
    •  & Peter R. Schofield
  110. Department of Pathology and Cell Biology, Columbia University Medical Center, New York 10032, USA.

    • Xinmin Liu
  111. Lymphocyte Cell Biology Unit, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.

    • Dan L. Longo
  112. Department of Psychiatry, Ludwig-Maximilians-Universität, Munich 80336, Germany.

    • Eva Meisenzahl
    •  & Dan Rujescu
  113. Department of Statistics & WMG, University of Warwick, Coventry CV4 7AL, UK.

    • Thomas E. Nichols
  114. Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.

    • Kazutaka Ohi
  115. Institute of Psychiatry, King’s College London, London SE5 8AF, UK.

    • Rocio Perez-Iglesias
  116. Department of Neurology, University of Calgary, Calgary T2N 2T9, Canada.

    • G. Bruce Pike
  117. Department of Clinical Neuroscience, University of Calgary, Calgary T2N 2T9, Canada.

    • G. Bruce Pike
  118. Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA.

    • Steven G. Potkin
  119. Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.

    • Glenn D. Rosen
  120. Harvard Medical School, Boston, Massachusetts 02115, USA.

    • Glenn D. Rosen
  121. Department of General Psychiatry, Heidelberg University Hospital, Heidelberg 69115, Germany.

    • Knut Schnell
  122. Department of Neuropathology, MRC Sudden Death Brain Bank Project, University of Edinburgh, Edinburgh EH8 9AG, UK.

    • Colin Smith
  123. Laboratory of Neuro Imaging, Institute for Neuroimaging and Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California 90033, USA.

    • Arthur W. Toga
  124. Department of Pathology, Johns Hopkins University, Baltimore, Maryland 21287, USA.

    • Juan Troncoso
  125. Psychology Department and Neuroscience Institute, Georgia State University, Atlanta, Georgia 30302, USA.

    • Jessica A. Turner
  126. Genentech, South San Francisco, California 94080, USA

    • Marcel van der Brug
  127. Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands.

    • Nic J. A. van der Wee
  128. Neuroimaging Centre, University of Groningen, University Medical Center Groningen, Groningen 9713 AW, The Netherlands.

    • Marie-Jose van Tol
  129. Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.

    • Thomas H. Wassink
  130. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm SE-141 83, Sweden.

    • Eric Westman
  131. Behavioral Epidemiology Section, National Institute on Aging Intramural Research Program, Baltimore, Maryland 20892, USA.

    • Alan B. Zonderman
  132. Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.

    • David G. Ashbrook
    •  & Reinmar Hager
  133. Center for Integrative and Translational Genomics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.

    • Lu Lu
    •  & Robert W. Williams
  134. Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.

    • Lu Lu
    •  & Robert W. Williams
  135. Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong 226001, China.

    • Lu Lu
  136. Cognitive Genetics and Therapy Group, School of Psychology & Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland.

    • Derek W. Morris
    •  & Gary Donohoe
  137. Department of Clinical Genetics, Maastricht University Medical Center, Maastricht 6200 MD, The Netherlands.

    • Han G. Brunner
  138. Department of Psychology, Center for Brain Science, Harvard University, Boston, Massachusetts 02138, USA.

    • Randy L. Buckner
  139. Karakter Child and Adolescent Psychiatry, Radboud university medical center, Nijmegen 6500 HB, The Netherlands.

    • Jan K. Buitelaar
  140. The Mind Research Network & LBERI, Albuquerque, New Mexico 87106, USA.

    • Vince D. Calhoun
  141. Department of ECE, University of New Mexico, Albuquerque, New Mexico 87131, USA.

    • Vince D. Calhoun
  142. Center for Translational Imaging and Personalized Medicine, University of California, San Diego, California 92093, USA.

    • Anders M. Dale
  143. Departments of Neurosciences, Radiology, Psychiatry, and Cognitive Science, University of California, San Diego, California 92093, USA.

    • Anders M. Dale
  144. Avera Institute for Human Genetics, Sioux Falls, South Dakota, 57108, USA.

    • Gareth E. Davies
  145. Neurology Division, Beaumont Hospital, Dublin 9, Ireland.

    • Norman Delanty
  146. Department of Neurology, Hopital Erasme, Universite Libre de Bruxelles, Brussels 1070, Belgium.

    • Chantal Depondt
    •  & Massimo Pandolfo
  147. Department of Medical Genetics, Oslo University Hospital, Oslo 0450, Norway.

    • Srdjan Djurovic
  148. Janssen Research & Development, Johnson & Johnson, Titusville, New Jersey 08560, USA.

    • Wayne C. Drevets
  149. Department of Psychiatry, University of Iowa, Iowa City, Iowa 52242, USA.

    • Beng-Choon Ho
  150. Munich Cluster for Systems Neurology (SyNergy), Munich 81377, Germany.

    • Bertram Müller-Myhsok
  151. University of Liverpool, Institute of Translational Medicine, Liverpool L69 3BX, UK.

    • Bertram Müller-Myhsok
  152. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald 17475, Germany.

    • Matthias Nauck
  153. Center for Imaging of Neurodegenerative Disease, San Francisco VA Medical Center, University of California, San Francisco, California 94121, USA.

    • Michael W. Weiner
  154. Department of Child and Adolescent Psychiatry, Erasmus University Medical Centre, Rotterdam 3000 CB, The Netherlands.

    • Tonya White
  155. Department of Radiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands.

    • Tonya White
    • , Hieab H. H. Adams
    •  & M. Arfan Ikram
  156. Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm SE-171 76, Sweden.

    • Ingrid Agartz
    •  & Erik G. Jönsson
  157. Clinical Neuroimaging Laboratory, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.

    • Dara M. Cannon
    •  & Colm McDonald
  158. Department of Psychiatry and Psychotherapy, HELIOS Hospital Stralsund 18435, Germany.

    • Hans J. Grabe
  159. Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University, Osaka 565-0871, Japan.

    • Ryota Hashimoto
  160. Medical University of Lodz, Lodz 90-419, Poland.

    • Iwona Kloszewska
  161. Department of Psychiatry, University of Oxford, Oxford OX3 7JX, UK.

    • Simon Lovestone
  162. NIHR Dementia Biomedical Research Unit, King’s College London, London SE5 8AF, UK.

    • Simon Lovestone
  163. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

    • Venkata S. Mattay
  164. Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia 06156, Italy.

    • Patrizia Mecocci
  165. Rotman Research Institute, University of Toronto, Toronto M6A 2E1, Canada.

    • Tomas Paus
  166. Departments of Psychology and Psychiatry, University of Toronto, Toronto M5T 1R8, Canada.

    • Tomas Paus
  167. Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto M5S 3E2, Canada.

    • Zdenka Pausova
  168. Neuropsychiatric Institute, Prince of Wales Hospital, Sydney 2031, Australia.

    • Perminder S. Sachdev
  169. Department of Neuroimaging, Institute of Psychiatry, King’s College London, London SE5 8AF, UK.

    • Andy Simmons
  170. Biomedical Research Centre for Mental Health, King’s College London, London SE5 8AF, UK.

    • Andy Simmons
  171. Biomedical Research Unit for Dementia, King’s College London, London SE5 8AF, UK.

    • Andy Simmons
  172. Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio FI-70211, Finland.

    • Hilkka Soininen
  173. Neurocentre Neurology, Kuopio University Hospital, Kuopio FI-70211, Finland.

    • Hilkka Soininen
  174. Departments of Psychiatry, Neurology, Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

    • Daniel R. Weinberger
  175. Department of Epidemiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands.

    • Hieab H. H. Adams
    • , Sven J. van der Lee
    • , Cornelia M. van Duijn
    •  & M. Arfan Ikram
  176. Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, Maryland 20892, USA.

    • Lenore J. Launer
  177. Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz 8010, Austria.

    • Stephan Seiler
    •  & Reinhold Schmidt
  178. INSERM U897, University of Bordeaux, Bordeaux 33076, France.

    • Ganesh Chauhan
  179. Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.

    • Claudia L. Satizabal
    •  & Sudha Seshadri
  180. Framingham Heart Study, Framingham, Massachusetts 01702, USA.

    • Claudia L. Satizabal
  181. Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.

    • James T. Becker
    •  & Sudha Seshadri
  182. Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.

    • James T. Becker
  183. Department of Psychology, Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.

    • James T. Becker
  184. General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.

    • Lisa Yanek
  185. Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.

    • Maritza Ebling
    • , Bruce Fischl
    • , Douglas Greve
    •  & Louis N. Vinke
  186. Computer Science and AI Lab, Massachusetts Institute of Technology, Boston, Massachusetts 02141, USA.

    • Bruce Fischl
  187. Department of Neurology University of Washington, Seattle, Washington 98195, USA.

    • W. T. Longstreth Jr
  188. Institute of Molecular Biology and Biochemistry, Medical University Graz, 8010 Graz, Austria.

    • Helena Schmidt
  189. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

    • Paul Nyquist
  190. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA.

    • Luting Xue
  191. Groupe d’Imagerie Neurofonctionnelle, UMR5296 CNRS, CEA and University of Bordeaux, Bordeaux 33076, France.

    • Bernard Mazoyer
  192. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington 98101, USA.

    • Joshua C. Bis
  193. Icelandic Heart Association, University of Iceland, Faculty of Medicine, Reykjavik 101, Iceland.

    • Vilmundur Gudnason

Consortia

  1. The Alzheimer’s Disease Neuroimaging Initiative

    A list of authors and affiliations appears in the Supplementary Information.

  2. The CHARGE Consortium

    A list of authors and affiliations appears in the Supplementary Information.

  3. EPIGEN

    A list of authors and affiliations appears in the Supplementary Information.

  4. IMAGEN

    A list of authors and affiliations appears in the Supplementary Information.

  5. SYS

    A list of authors and affiliations appears in the Supplementary Information.

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Contributions

Individual author contributions are listed in Supplementary Note 4.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Paul M. Thompson or Sarah E. Medland.

Summary statistics from GWAS results are available online using the ENIGMA-Vis web tool: http://enigma.ini.usc.edu/enigma-vis/.

Extended data

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains authorship information regarding all the authors, contributing consortia authors, acknowledgements of funding sources and a list of author contributions. This file was replaced on 8 April 2015 to reflect changes to the IMAGEN and ADNI consortia lists.

Excel files

  1. 1.

    Supplementary Tables

    This file contains Supplementary Tables 1-9, detailing site-specific demographics and methods, consistency of MRI segmentation across software, independent genome-wide significant SNPs and genes, generalization sample association results, and look-ups of previous candidate gene associations.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nature14101

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