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Abstract
Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers—the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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; van der Meer Dennis 2
; Moreau, Clara 3
; Kaufmann, Tobias 4
; Bragi, Walters G 5
; Ellegaard, Maria 6 ; Abdellaoui Abdel 7
; Ames, David 8 ; Amunts Katrin 9
; Andersson Micael 10 ; Armstrong, Nicola J 11
; Bernard, Manon 12 ; Blackburn, Nicholas B 13
; Blangero, John 13
; Boomsma Dorret I 14
; Brodaty Henry 15
; Brouwer, Rachel M 16 ; Bülow, Robin 17
; Bøen Rune 18 ; Cahn Wiepke 19
; Calhoun, Vince D 20 ; Caspers Svenja 21 ; Ching Christopher R K 22 ; Cichon Sven 23
; Ciufolini Simone 24 ; Crespo-Facorro Benedicto 25 ; Curran, Joanne E 13 ; Dale, Anders M 26 ; Dalvie Shareefa 27
; Dazzan Paola 28
; de Geus Eco J C 14
; Greig, de Zubicaray, I 29
; de Zwarte Sonja M C 16 ; Sylvane, Desrivieres 30
; Doherty, Joanne L 31 ; Donohoe, Gary 32 ; Draganski Bogdan 33
; Ehrlich, Stefan 34 ; Eising Else 35
; Espeseth, Thomas 36 ; Fejgin, Kim 37 ; Fisher, Simon E 38
; Fladby Tormod 39 ; Frei Oleksandr 40 ; Frouin Vincent 41
; Fukunaga Masaki 42 ; Gareau, Thomas 41 ; Tian, Ge 43 ; Glahn, David C 44 ; Grabe, Hans J 45
; Groenewold, Nynke A 27 ; Ómar, Gústafsson 46 ; Haavik, Jan 47
; Haberg, Asta K 48 ; Hall, Jeremy 49
; Hashimoto Ryota 50 ; Hehir-Kwa, Jayne Y 51 ; Hibar, Derrek P 52 ; Hillegers Manon H J 53
; Hoffmann, Per 54
; Holleran Laurena 32 ; Holmes, Avram J 55
; Homuth Georg 56 ; Jouke-Jan, Hottenga 14
; Hulshoff Pol Hilleke E 16 ; Ikeda Masashi 57
; Jahanshad Neda 22
; Jockwitz Christiane 21 ; Johansson, Stefan 58
; Jönsson, Erik G 59 ; Jørgensen, Niklas R 60 ; Kikuchi Masataka 61
; Knowles Emma E M 62 ; Kumar, Kuldeep 63
; Le Hellard Stephanie 64
; Leu Costin 65 ; Linden David E J 66 ; Liu, Jingyu 67
; Lundervold Arvid 68 ; Lundervold Astri Johansen 69
; Maillard, Anne M 70
; Martin, Nicholas G 71 ; Martin-Brevet, Sandra 72 ; Mather, Karen A 73
; Mathias, Samuel R 62 ; McMahon, Katie L 74
; McRae, Allan F 75
; Medland, Sarah E 76
; Meyer-Lindenberg, Andreas 77 ; Moberget Torgeir 78 ; Modenato, Claudia 79
; Sánchez, Jennifer Monereo 80
; Morris, Derek W 32
; Mühleisen, Thomas W 81
; Murray, Robin M 82
; Nielsen, Jacob 37 ; Nordvik, Jan E 83 ; Nyberg, Lars 84 ; Loohuis Loes M Olde 85
; Ophoff, Roel A 86
; Owen, Michael J 87
; Paus Tomas 88
; Pausova Zdenka 89
; Peralta, Juan M 13
; Bruce, Pike G 90
; Prieto, Carlos 91
; Quinlan, Erin B 92
; Reinbold, Céline S 93 ; Marques, Tiago Reis 94
; Rucker James J H 95
; Sachdev, Perminder S 96
; Sando, Sigrid B 97 ; Schofield, Peter R 98
; Schork, Andrew J 99
; Schumann Gunter 92
; Shin, Jean 89
; Shumskaya Elena 100 ; Silva, Ana I 101
; Sisodiya, Sanjay M 102 ; Steen, Vidar M 64 ; Stein, Dan J 103
; Strike, Lachlan T 104
; Suzuki, Ikuo K 105 ; Tamnes, Christian K 106
; Teumer, Alexander 107
; Thalamuthu Anbupalam 108 ; Tordesillas-Gutiérrez, Diana 109
; Uhlmann, Anne 27 ; Ulfarsson, Magnus O 110
; van ‘t Ent Dennis 111 ; van den Bree Marianne B M 49
; Vanderhaeghen Pierre 112
; Vassos Evangelos 113
; Wen, Wei 108
; Wittfeld Katharina 45
; Wright, Margaret J 114
; Agartz Ingrid 115 ; Djurovic Srdjan 116
; Westlye, Lars T 117
; Stefansson Hreinn 46
; Stefansson Kari 5
; Jacquemont Sébastien 118
; Thompson, Paul M 22 ; Andreassen, Ole A 119
1 Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, NORMENT, Division of Mental Health and Addiction, Oslo, Norway; Oslo University Hospital, Department of Medical Genetics, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485); University of Oslo, KG Jebsen Centre for Neurodevelopmental Disorders, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921)
2 Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, NORMENT, Division of Mental Health and Addiction, Oslo, Norway (GRID:grid.5510.1); Medicine and Life Sciences, Maastricht University, School of Mental Health and Neuroscience, Faculty of Health, Maastricht, the Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099)
3 Sainte Justine Hospital Research Center, Montreal, Quebec, Canada (GRID:grid.411418.9) (ISNI:0000 0001 2173 6322); Centre de recherche de l’Institut universitaire de gériatrie de Montréal, Montreal, Quebec, Canada (GRID:grid.294071.9) (ISNI:0000 0000 9199 9374)
4 Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, NORMENT, Division of Mental Health and Addiction, Oslo, Norway (GRID:grid.294071.9); University of Tübingen, Department of Psychiatry and Psychotherapy, Tübingen, Germany (GRID:grid.10392.39) (ISNI:0000 0001 2190 1447)
5 deCODE Genetics (Amgen), Reykjavík, Iceland (GRID:grid.421812.c) (ISNI:0000 0004 0618 6889); University of Iceland, Faculty of Medicine, Reykjavík, Iceland (GRID:grid.14013.37) (ISNI:0000 0004 0640 0021)
6 Copenhagen University Hospital, Department of Clinical Biochemistry, Rigshospitalet, Denmark (GRID:grid.4973.9) (ISNI:0000 0004 0646 7373)
7 University of Amsterdam, Department of Psychiatry, Amsterdam UMC, Amsterdam, the Netherlands (GRID:grid.7177.6) (ISNI:0000000084992262); VU University Amsterdam, Department of Biological Psychology and Netherlands Twin Register, Amsterdam, the Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227)
8 University of Melbourne Academic Unit for Psychiatry of Old Age, Kew, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X); National Ageing Research Institute, Parkville, Australia (GRID:grid.429568.4) (ISNI:0000 0004 0382 5980)
9 INM-1, Research Centre Jülich, Institute of Neuroscience and Medicine, Jülich, Germany (GRID:grid.8385.6) (ISNI:0000 0001 2297 375X); University Hospital Düsseldorf, Heinrich Heine University Duesseldorf, C. and O. Vogt Institute for Brain Research, Medical Faculty, Düsseldorf, Germany (GRID:grid.8385.6)
10 Umeå University, Umeå Centre for Functional Brain Imaging, Umeå, Sweden (GRID:grid.12650.30) (ISNI:0000 0001 1034 3451); Umeå University, Department of Integrative Medical Biology, Umeå, Sweden (GRID:grid.12650.30) (ISNI:0000 0001 1034 3451)
11 Murdoch University, Mathematics and Statistics, Perth, Australia (GRID:grid.1025.6) (ISNI:0000 0004 0436 6763)
12 Hospital for Sick Children, Research Institute, Toronto, Canada (GRID:grid.42327.30) (ISNI:0000 0004 0473 9646)
13 University of Texas Rio Grande Valley, South Texas Diabetes and Obesity Institute, Department of Human Genetics, School of Medicine, Brownsville, USA (GRID:grid.449717.8) (ISNI:0000 0004 5374 269X)
14 VU University Amsterdam, Department of Biological Psychology and Netherlands Twin Register, Amsterdam, the Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227); Amsterdam Neuroscience, Amsterdam, the Netherlands (GRID:grid.484519.5); Amsterdam Public Health Research Institute, VU Medical Center, Amsterdam, the Netherlands (GRID:grid.16872.3a) (ISNI:0000 0004 0435 165X)
15 University of New South Wales, Centre for Healthy Brain Ageing, School of Psychiatry, Sydney, Australia (GRID:grid.1005.4) (ISNI:0000 0004 4902 0432); University of New South Wales, Dementia Centre for Research Collaboration, School of Psychiatry, Sydney, Australia (GRID:grid.1005.4) (ISNI:0000 0004 4902 0432)
16 University Medical Center Brain Center, Utrecht University, Department of Psychiatry, Utrecht, the Netherlands (GRID:grid.5477.1) (ISNI:0000000120346234)
17 University Medicine Greifswald, Institute of Diagnostic Radiology and Neuroradiology, Greifswald, Germany (GRID:grid.5603.0)
18 Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, NORMENT, Division of Mental Health and Addiction, Oslo, Norway (GRID:grid.5603.0); Oslo University Hospital, Department of Medical Genetics, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485)
19 University Medical Center Brain Center, Utrecht University, Department of Psychiatry, Utrecht, the Netherlands (GRID:grid.5477.1) (ISNI:0000000120346234); Altrecht Science, Utrecht, the Netherlands (GRID:grid.5477.1)
20 Georgia State University, Georgia Institute of Technology, Emory University, Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Atlanta, USA (GRID:grid.5477.1); University of New Mexico, The Department of Electrical and Computer Engineering, Albuquerque, USA (GRID:grid.266832.b) (ISNI:0000 0001 2188 8502)
21 INM-1, Research Centre Jülich, Institute of Neuroscience and Medicine, Jülich, Germany (GRID:grid.8385.6) (ISNI:0000 0001 2297 375X); Heinrich Heine University Düsseldorf, Institute for Anatomy I, Medical Faculty, Düsseldorf, Germany (GRID:grid.411327.2) (ISNI:0000 0001 2176 9917)
22 University of Southern California, Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853)
23 INM-1, Research Centre Jülich, Institute of Neuroscience and Medicine, Jülich, Germany (GRID:grid.8385.6) (ISNI:0000 0001 2297 375X); University of Basel, Department of Biomedicine, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642); University Hospital Basel, Institute of Medical Genetics and Pathology, Basel, Switzerland (GRID:grid.410567.1)
24 King’s College London, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, London, United Kingdom (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764)
25 University Hospital Marqués de Valdecilla, IDIVAL, Centro de Investigación Biomédica en Red Salud Mental (CIBERSAM), Santander, Spain (GRID:grid.411325.0) (ISNI:0000 0001 0627 4262); University Hospital Virgen del Rocío, IBiS, Centre de Investigació Biomédica en Red Salud Mental (CIBERSAM), Sevilla, Spain (GRID:grid.411109.c) (ISNI:0000 0000 9542 1158)
26 University of California, Center for Multimodal Imaging and Genetics, San Diego, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242)
27 University of Cape Town, Department of Psychiatry and Neuroscience Institute, Cape Town, South Africa (GRID:grid.7836.a) (ISNI:0000 0004 1937 1151)
28 Psychology and Neuroscience, King’s College London, Department of Psychological Medicine, Institute of Psychiatry, London, United Kingdom (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764)
29 Queensland University of Technology, Faculty of Health, Brisbane, Australia (GRID:grid.1024.7) (ISNI:0000000089150953)
30 Psychology and Neuroscience, King’s College London, Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, London, United Kingdom (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764)
31 Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff, United Kingdom (GRID:grid.5600.3) (ISNI:0000 0001 0807 5670); Cardiff University, Cardiff University Brain Research Imaging Centre School of Psychology, Cardiff, United Kingdom (GRID:grid.5600.3) (ISNI:0000 0001 0807 5670)
32 National University of Ireland Galway, Centre for Neuroimaging and Cognitive Genomics, School of Psychology and Discipline of Biochemistry, Galway, Ireland (GRID:grid.6142.1) (ISNI:0000 0004 0488 0789)
33 Lausanne University Hospital and University of Lausanne, Laboratory for Research in Neuroimaging LREN, Centre for Research in Neurosciences, Department of Clinical Neurosciences, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662); Max-Planck-Institute for Human Cognitive and Brain Sciences, Neurology Department, Leipzig, Germany (GRID:grid.419524.f) (ISNI:0000 0001 0041 5028)
34 Faculty of Medicine, TU Dresden, Division of Psychological and Social Medicine, Dresden, Germany (GRID:grid.4488.0) (ISNI:0000 0001 2111 7257)
35 Max Planck Institute for Psycholinguistics, Language and Genetics Department, Nijmegen, the Netherlands (GRID:grid.419550.c) (ISNI:0000 0004 0501 3839)
36 University of Oslo, Department of Psychology, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921); Bjørknes College, Oslo, Norway (GRID:grid.5510.1)
37 Signal Transduction, H. Lundbeck A/S, Valby, Denmark (GRID:grid.424580.f) (ISNI:0000 0004 0476 7612)
38 Max Planck Institute for Psycholinguistics, Language and Genetics Department, Nijmegen, the Netherlands (GRID:grid.419550.c) (ISNI:0000 0004 0501 3839); Radboud University, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands (GRID:grid.5590.9) (ISNI:0000000122931605)
39 Akershus University Hospital, Department of Neurology, Nordbyhagen, Norway (GRID:grid.411279.8) (ISNI:0000 0000 9637 455X); University of Oslo, Institute of Clinical Medicine, Campus Ahus, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921)
40 Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, NORMENT, Division of Mental Health and Addiction, Oslo, Norway (GRID:grid.5510.1)
41 Université Paris-Saclay, CEA, Neurospin, Gif-sur-Yvette, France (GRID:grid.457334.2)
42 National Institute for Physiological Sciences, Division of Cerebral Integration, Okazaki, Japan (GRID:grid.467811.d) (ISNI:0000 0001 2272 1771); Department of Life Science, Sokendai, Hayama, Japan (GRID:grid.275033.0) (ISNI:0000 0004 1763 208X)
43 Massachusetts General Hospital, Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Harvard Medical School, Department of Psychiatry, Massachusetts General Hospital, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, USA (GRID:grid.66859.34)
44 Boston Children’s Hospital, Boston, USA (GRID:grid.2515.3) (ISNI:0000 0004 0378 8438); Institute of Living, Hartford, USA (GRID:grid.277313.3) (ISNI:0000 0001 0626 2712); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)
45 University Medicine Greifswald, Department of Psychiatry and Psychotherapy, Greifswald, Germany (GRID:grid.5603.0); German Center of Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Greifswald, Germany (GRID:grid.424247.3) (ISNI:0000 0004 0438 0426)
46 deCODE Genetics (Amgen), Reykjavík, Iceland (GRID:grid.421812.c) (ISNI:0000 0004 0618 6889)
47 University of Bergen, Department of Biomedicine, Bergen, Norway (GRID:grid.7914.b) (ISNI:0000 0004 1936 7443); Haukeland University Hospital, Division of Psychiatry, Bergen, Norway (GRID:grid.412008.f) (ISNI:0000 0000 9753 1393)
48 Norwegian University of Science and Technology, Department of Neuromedicine and Movement Science, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393); St Olav’s Hospital, Department of Radiology and Nuclear Medicine, Trondheim, Norway (GRID:grid.52522.32) (ISNI:0000 0004 0627 3560)
49 Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff, United Kingdom (GRID:grid.5600.3) (ISNI:0000 0001 0807 5670); Cardiff University, School of Medicine, Cardiff, United Kingdom (GRID:grid.5600.3) (ISNI:0000 0001 0807 5670)
50 National Center of Neurology and Psychiatry, Department of Pathology of Mental Diseases, National Institute of Mental Health, Kodaira, Japan (GRID:grid.419280.6) (ISNI:0000 0004 1763 8916); Osaka University, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971)
51 Princess Màxima Center for Pediatric Oncology, Utrecht, the Netherlands (GRID:grid.487647.e)
52 Genentech, Inc., South San Francisco, USA (GRID:grid.418158.1) (ISNI:0000 0004 0534 4718)
53 Erasmus MC-Sophia, Department of Child and Adolescent Psychiatry/Psychology, Rotterdam, the Netherlands (GRID:grid.416135.4)
54 University Hospital Basel, Institute of Medical Genetics and Pathology, Basel, Switzerland (GRID:grid.410567.1); University of Bonn Medical School, Institute of Human Genetics, Bonn, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300)
55 Yale University, Psychology Department, New Haven, USA (GRID:grid.47100.32) (ISNI:0000000419368710); Yale University, Department of Psychiatry, New Haven, USA (GRID:grid.47100.32) (ISNI:0000000419368710); Massachusetts General Hospital, Department of Psychiatry, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924)
56 University Medicine Greifswald, Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany (GRID:grid.5603.0)
57 Fujita Health University School of Medicine, Department of Psychiatry, Toyoake, Japan (GRID:grid.256115.4) (ISNI:0000 0004 1761 798X)
58 University of Bergen, Department of Clinical Science, Bergen, Norway (GRID:grid.7914.b) (ISNI:0000 0004 1936 7443); Haukeland University Hospital, Department of Medical Genetics, Bergen, Norway (GRID:grid.412008.f) (ISNI:0000 0000 9753 1393)
59 Karolinska Institutet, & Stockholm Health Care Services, Stockholm Region, Centre for Psychiatry Research, Department of Clinical Neuroscience, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); University of Oslo, Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921)
60 Copenhagen University Hospital Rigshospitalet, Department of Clinical Biochemistry, Glostrup, Denmark (GRID:grid.475435.4); University of Copenhagen, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X)
61 Osaka University, Department of Genome Informatics, Graduate School of Medicine, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971)
62 Boston Children’s Hospital, Boston, USA (GRID:grid.2515.3) (ISNI:0000 0004 0378 8438); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)
63 Sainte Justine Hospital Research Center, Montreal, Quebec, Canada (GRID:grid.411418.9) (ISNI:0000 0001 2173 6322)
64 University of Bergen, Norwegian Centre for Mental Disorders Research, Department of Clinical Science, Bergen, Norway (GRID:grid.7914.b) (ISNI:0000 0004 1936 7443); Haukeland University Hospital, Dr Einar Martens Research Group for Biological Psychiatry, Department of Medical Genetics, Bergen, Norway (GRID:grid.412008.f) (ISNI:0000 0000 9753 1393)
65 Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, USA (GRID:grid.66859.34); UCL Queen Square Institute of Neurology, Department of Clinical and Experimental Epilepsy, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201); Lerner Research Institute, Cleveland Clinic, Cleveland, Genomic Medicine Institute, Ohio, United States (GRID:grid.239578.2) (ISNI:0000 0001 0675 4725); Chalfont Centre for Epilepsy, Chalfont-St-Peter, United Kingdom (GRID:grid.452379.e) (ISNI:0000 0004 0386 7187)
66 Medicine and Life Sciences, Maastricht University, School of Mental Health and Neuroscience, Faculty of Health, Maastricht, the Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099); Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff, United Kingdom (GRID:grid.5600.3) (ISNI:0000 0001 0807 5670)
67 Georgia State University, Georgia Institute of Technology, Emory University, Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Atlanta, USA (GRID:grid.5600.3)
68 University of Bergen, Department of Biomedicine, Bergen, Norway (GRID:grid.7914.b) (ISNI:0000 0004 1936 7443); Haukeland University Hospital, Mohn Medical Imaging and Visualization Centre, Department of Radiology, Bergen, Norway (GRID:grid.412008.f) (ISNI:0000 0000 9753 1393)
69 University of Bergen, Department of Biological and Medical Psychology, Bergen, Norway (GRID:grid.7914.b) (ISNI:0000 0004 1936 7443)
70 Lausanne University Hospital, Service des Troubles du Spectre de l’Autisme et apparentés, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662)
71 QIMR Berghofer Medical Research Institute, Genetic Epidemiology, Brisbane, Australia (GRID:grid.1049.c) (ISNI:0000 0001 2294 1395)
72 Lausanne University Hospital and University of Lausanne, Laboratory for Research in Neuroimaging LREN, Centre for Research in Neurosciences, Department of Clinical Neurosciences, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662)
73 University of New South Wales, Centre for Healthy Brain Ageing, School of Psychiatry, Sydney, Australia (GRID:grid.1005.4) (ISNI:0000 0004 4902 0432); Neuroscience Research Australia, Randwick, Australia (GRID:grid.250407.4) (ISNI:0000 0000 8900 8842)
74 Queensland University of Technology, Herston Imaging Research Facility and School of Clinical Sciences, Brisbane, Australia (GRID:grid.1024.7) (ISNI:0000000089150953)
75 University of Queensland, Institute for Molecular Bioscience, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); University of Queensland, Queensland Brain Institute, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537)
76 QIMR Berghofer Medical Research Institute, Psychiatric Genetics, Brisbane, Australia (GRID:grid.1049.c) (ISNI:0000 0001 2294 1395)
77 University of Heidelberg, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Mannheim, Germany (GRID:grid.7700.0) (ISNI:0000 0001 2190 4373)
78 Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, NORMENT, Division of Mental Health and Addiction, Oslo, Norway (GRID:grid.7700.0); University of Oslo, Department of Psychology, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921)
79 Lausanne University Hospital and University of Lausanne, Laboratory for Research in Neuroimaging LREN, Centre for Research in Neurosciences, Department of Clinical Neurosciences, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662); University of Lausanne, Lausanne, Switzerland (GRID:grid.9851.5) (ISNI:0000 0001 2165 4204)
80 Maastricht University Medical Center, Department of Radiology and Nuclear Medicine, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382); Maastricht University, School for Mental Health and Neuroscience, Maastricht, the Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099)
81 INM-1, Research Centre Jülich, Institute of Neuroscience and Medicine, Jülich, Germany (GRID:grid.8385.6) (ISNI:0000 0001 2297 375X); University Hospital Düsseldorf, Heinrich Heine University Duesseldorf, C. and O. Vogt Institute for Brain Research, Medical Faculty, Düsseldorf, Germany (GRID:grid.8385.6); University of Basel, Department of Biomedicine, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642)
82 King’s College London, Institute of Psychiatry, Psychology and Neuroscience, London, United Kingdom (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764)
83 The CatoSenteret Rehabilitation Center, Son, Norway (GRID:grid.424580.f)
84 Umeå University, Umeå Centre for Functional Brain Imaging, Umeå, Sweden (GRID:grid.12650.30) (ISNI:0000 0001 1034 3451); Umeå University, Department of Integrative Medical Biology, Umeå, Sweden (GRID:grid.12650.30) (ISNI:0000 0001 1034 3451); Umeå University, Department of Radiation Sciences, Umeå, Sweden (GRID:grid.12650.30) (ISNI:0000 0001 1034 3451)
85 University of California, Center for Neurobehavioral Genetics, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718)
86 University of California, Center for Neurobehavioral Genetics, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718); Erasmus University Medical Center, Department of Psychiatry, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X)
87 Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff, United Kingdom (GRID:grid.5600.3) (ISNI:0000 0001 0807 5670)
88 Holland Bloorview Kids Rehabilitation Hospital, Toronto, Bloorview Research Institute, Ontario, Canada (GRID:grid.414294.e) (ISNI:0000 0004 0572 4702); University of Toronto, Toronto, Physiology and Nutritional Sciences, Ontario, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938)
89 Hospital for Sick Children, Research Institute, Toronto, Canada (GRID:grid.42327.30) (ISNI:0000 0004 0473 9646); University of Toronto, Toronto, Physiology and Nutritional Sciences, Ontario, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938)
90 University of Calgary, Departments of Radiology and Clinical Neurosciences, Calgary, Canada (GRID:grid.22072.35) (ISNI:0000 0004 1936 7697)
91 University of Salamanca, Bioinformatics Service, Nucleus, Salamanca, Spain (GRID:grid.11762.33) (ISNI:0000 0001 2180 1817)
92 Psychology and Neuroscience, King’s College London, Centre for Population Neuroscience and Precision Medicine, Institute of Psychiatry, London, United Kingdom (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764)
93 University of Basel, Department of Biomedicine, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642); University Hospital Basel, Institute of Medical Genetics and Pathology, Basel, Switzerland (GRID:grid.410567.1); University of Oslo, Department of Psychology, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921)
94 Psychology & Neuroscience, Kings College, Department of Psychosis, Institute of Psychiatry, London, United Kingdom (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764); Imperial College, Psychiatric Imaging Group, MRC London Institute of Medical Sciences (LMS), Hammersmith Hospital, London, United Kingdom (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111)
95 Psychology and Neuroscience, London, Institute of Psychiatry, London, United Kingdom (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764)
96 University of New South Wales, Centre for Healthy Brain Ageing, School of Psychiatry, Sydney, Australia (GRID:grid.1005.4) (ISNI:0000 0004 4902 0432); The Prince of Wales Hospital, Neuropsychiatric Institute, Sydney, Australia (GRID:grid.415193.b)
97 Norwegian University of Science and Technology, Department of Neuromedicine and Movement Science, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393); University Hospital of Trondheim,Department of Neurology and Clinical Neurophysiology, Trondheim, Norway (GRID:grid.52522.32) (ISNI:0000 0004 0627 3560)
98 Neuroscience Research Australia, Sydney, Australia (GRID:grid.250407.4) (ISNI:0000 0000 8900 8842); University of New South Wales, School of Medical Sciences, Sydney, Australia (GRID:grid.1005.4) (ISNI:0000 0004 4902 0432)
99 Institute of Biological Psychiatry, Roskilde, Denmark (GRID:grid.1005.4); The Translational Genetics Institute (TGEN), Phoenix, United States (GRID:grid.1005.4)
100 Radboud University, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands (GRID:grid.5590.9) (ISNI:0000000122931605); Radboud University Medical Center, Department of Human Genetics, Nijmegen, the Netherlands (GRID:grid.10417.33) (ISNI:0000 0004 0444 9382)
101 Medicine and Life Sciences, Maastricht University, School of Mental Health and Neuroscience, Faculty of Health, Maastricht, the Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099); Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff, United Kingdom (GRID:grid.5600.3) (ISNI:0000 0001 0807 5670); Cardiff University, Cardiff University Brain Research Imaging Centre School of Psychology, Cardiff, United Kingdom (GRID:grid.5600.3) (ISNI:0000 0001 0807 5670)
102 UCL Queen Square Institute of Neurology, Department of Clinical and Experimental Epilepsy, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201); Chalfont Centre for Epilepsy, Chalfont-St-Peter, United Kingdom (GRID:grid.452379.e) (ISNI:0000 0004 0386 7187)
103 University of Cape Town, South African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, Cape Town, South Africa (GRID:grid.7836.a) (ISNI:0000 0004 1937 1151)
104 University of Queensland, Queensland Brain Institute, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537)
105 Stem Cell and Developmental Neurobiology Lab, VIB Center for Brain & Disease Research, Leuven, Belgium (GRID:grid.1003.2); University of Brussels (ULB), Institute of Interdisciplinary Research (IRIBHM) ULB Neuroscience Institute, Brussels, Belgium (GRID:grid.8767.e) (ISNI:0000 0001 2290 8069); The University of Tokyo, Department of Biological Sciences, Graduate School of Science, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X)
106 Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, NORMENT, Division of Mental Health and Addiction, Oslo, Norway (GRID:grid.26999.3d); University of Oslo, PROMENTA Research Center, Department of Psychology, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921); Diakonhjemmet Hospital, Department of Psychiatry, Oslo, Norway (GRID:grid.413684.c) (ISNI:0000 0004 0512 8628)
107 University Medicine Greifswald, Institute for Community Medicine, Greifswald, Germany (GRID:grid.5603.0)
108 University of New South Wales, Centre for Healthy Brain Ageing, School of Psychiatry, Sydney, Australia (GRID:grid.1005.4) (ISNI:0000 0004 4902 0432)
109 University Hospital Marqués de Valdecilla, IDIVAL, Centro de Investigación Biomédica en Red Salud Mental (CIBERSAM), Santander, Spain (GRID:grid.411325.0) (ISNI:0000 0001 0627 4262); Marqués de Valdecilla University Hospital, Valdecilla Biomedical Research Institute IDIVAL, Department of Radiology, Santander, Spain (GRID:grid.411325.0) (ISNI:0000 0001 0627 4262)
110 deCODE Genetics (Amgen), Reykjavík, Iceland (GRID:grid.421812.c) (ISNI:0000 0004 0618 6889); University of Iceland, Faculty of Electrical and Computer Engineering, Reykjavík, Iceland (GRID:grid.14013.37) (ISNI:0000 0004 0640 0021)
111 VU University Amsterdam, Department of Biological Psychology and Netherlands Twin Register, Amsterdam, the Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227); Amsterdam Neuroscience, Amsterdam, the Netherlands (GRID:grid.484519.5)
112 VIB-KU Leuven Center for Brain & Disease Research, Leuven, Belgium (GRID:grid.5600.3); KU Leuven, Department of Neurosciences & Leuven Brain Institute, Leuven, Belgium (GRID:grid.5596.f) (ISNI:0000 0001 0668 7884); Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), Université Libre de Bruxelles (U.L.B.), Brussels, Belgium (GRID:grid.4989.c) (ISNI:0000 0001 2348 0746)
113 King’s College London, Institute of Psychiatry, Psychology and Neuroscience, London, United Kingdom (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764); South London and Maudsley National Health Service Foundation Trust and King’s College London, National Institute for Health Research, Mental Health Biomedical Research Centre, London, United Kingdom (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764)
114 University of Queensland, Queensland Brain Institute, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); University of Queensland, Centre for Advanced Imaging, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537)
115 Karolinska Institutet, & Stockholm Health Care Services, Stockholm Region, Centre for Psychiatry Research, Department of Clinical Neuroscience, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); University of Oslo, Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921); Diakonhjemmet Hospital, Department of Psychiatry, Oslo, Norway (GRID:grid.413684.c) (ISNI:0000 0004 0512 8628)
116 Oslo University Hospital, Department of Medical Genetics, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485); University of Bergen, Norwegian Centre for Mental Disorders Research, Department of Clinical Science, Bergen, Norway (GRID:grid.7914.b) (ISNI:0000 0004 1936 7443)
117 Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, NORMENT, Division of Mental Health and Addiction, Oslo, Norway (GRID:grid.7914.b); University of Oslo, KG Jebsen Centre for Neurodevelopmental Disorders, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921); University of Oslo, Department of Psychology, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921)
118 Sainte Justine Hospital Research Center, Montreal, Quebec, Canada (GRID:grid.411418.9) (ISNI:0000 0001 2173 6322); University of Montreal, Montreal, Department of Pediatrics, Quebec, Canada (GRID:grid.14848.31) (ISNI:0000 0001 2292 3357)
119 Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, NORMENT, Division of Mental Health and Addiction, Oslo, Norway (GRID:grid.42505.36)




