doi: 10.1016/j.bpsc.2025.05.010.
Online ahead of print.
Penetrance of Neurodevelopmental Copy Number Variants Is Associated With Variations in Cortical Morphology
Ana I Silva
1
, Ida E Sønderby
2
, George Kirov
3
, Abdel Abdellaoui
4
, Ingrid Agartz
5
, David Ames
6
, Nicola J Armstrong
7
, Eric Artiges
8
, Tobias Banaschewski
9
, Anne S Bassett
10
, Carrie E Bearden
11
, John Blangero
12
, Rune Boen
13
, Dorret I Boomsma
14
, Robin Bülow
15
, Nancy J Butcher
16
, Vince Calhoun
17
, Linda E Campbell
18
, Eva W C Chow
19
, Simone Ciufolini
20
, Michael C Craig
21
, Benedicto Crespo-Farroco
22
, Adam C Cunningham
23
, Shareefa Dalvie
24
, Eileen Daly
25
, Paola Dazzan
26
, Eco J C de Geus
27
, Greig I de Zubicaray
28
, Joanne L Doherty
29
, Gary Donohoe
30
, Mark Drakesmith
31
, Thomas Espeseth
32
, Vincent Frouin
33
, Hugh Garavan
34
, David C Glahn
35
, Naomi J Goodrich-Hunsaker
36
, Penny A Gowland
37
, Hans J Grabe
38
, Antoine Grigis
33
, Maria Gudbrandsen
39
, Boris A Gutman
40
, Jan Haavik
41
, Asta K Håberg
42
, Jeremy Hall
3
, Andreas Heinz
43
, Sarah Hohmann
44
, Jouke-Jan Hottenga
45
, Sébastien Jacquemont
46
, Neda Jahanshad
47
, Rachel K Jonas
13
, Derek K Jones
48
, Erik G Jönsson
49
, Sanne Koops
50
, Kuldeep Kumar
51
, Stephanie Le Hellard
52
, Herve Lemaitre
53
, Jingyu Liu
54
, Astri J Lundervold
55
, Jean-Luc Martinot
56
, Karen A Mather
57
, Donna M McDonald-McGinn
58
, Katie L McMahon
59
, Allan F McRae
60
, Sarah E Medland
61
, Clara A Moreau
51
, Kieran C Murphy
62
, Declan Murphy
25
, Robin M Murray
20
, Frauke Nees
63
, Michael J Owen
3
, Marie-Laure Paillère Martinot
64
, Diimitri Papadopoulos Orfanos
33
, Tomas Paus
65
, Luise Poustka
66
, Tiago Reis Marques
67
, David R Roalf
68
, Perminder S Sachdev
69
, Freda Scheffler
70
, J Eric Schmitt
71
, Gunter Schumann
72
, Vidar M Steen
52
, Dan J Stein
73
, Lachlan T Strike
61
, Alexander Teumer
74
, Anbupalam Thalamuthu
75
, Sophia I Thomopoulos
47
, Diana Tordesillas-Gutiérrez
76
, Julian N Trollor
77
, Anne Uhlmann
78
, Ariana Vajdi
79
, Dennis van 't Ent
27
, Therese van Amelsvoort
80
, Marianne B M van den Bree
3
, Dennis van der Meer
81
, Javier Vázquez-Bourgon
82
, Julio E Villalón-Reina
47
, Uwe Völker
83
, Henry Völzke
84
, Jacob A S Vorstman
85
, Lars T Westlye
86
, Nigel Williams
23
, Katharina Wittfeld
38
, Margaret J Wright
87
, Paul M Thompson
47
, Ole A Andreassen
88
, David E J Linden
89
; ENIGMA-CNV Working Group
Affiliations
Affiliations
- 1 School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands; Neuroscience and Mental Health Innovation Institute, Cardiff University, Cardiff, United Kingdom; Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota. Electronic address: silvaai@umn.edu.
- 2 Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
- 3 Neuroscience and Mental Health Innovation Institute, Cardiff University, Cardiff, United Kingdom; Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom; Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, United Kingdom.
- 4 Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
- 5 Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm & Stockholm Health Care Services, Stockholm Region, Stockholm, Sweden; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
- 6 University of Melbourne Academic Unit for Psychiatry of Old Age, Kew, Victoria, Australia.
- 7 Mathematics and Statistics, Curtin University, Perth, Western Australia, Australia.
- 8 Institut National de la Santé et de la Recherche Médicale (INSERM) U1299 "Trajectoires développementales et psychiatrie" Université Paris-Saclay, Centre National de la Recherche Scientifique, Centre Borelli, Gif-sur-Yvette, France; Psychiatry Department, Établissement public de santé Barthélémy Durand, Étampes, Île-de-France, France.
- 9 Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
- 10 Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Dalglish Family 22q Clinic for Adults with 22q11.2 Deletion Syndrome, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
- 11 Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California; Department of Psychology, University of California, Los Angeles, California.
- 12 Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, Texas.
- 13 Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California.
- 14 Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Public Health Research Institute, Amsterdam UMC, Amsterdam, the Netherlands.
- 15 Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
- 16 Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
- 17 Tri-institutional Center for Translational Research in Neuroimaging and Data Science, Georgia State, Georgia Tech, Emory University, Atlanta, Georgia.
- 18 School of Psychological Science, University of Newcastle, Newcastle, New South Wales, Australia.
- 19 Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
- 20 Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
- 21 National Female Hormone Clinic, London, United Kingdom; Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
- 22 Centro de Investigación Biomédica en Red en Salud Mental, Sevilla, Spain; Instituto de Investigación Biomédica de Sevilla IBIS-CSIC, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Departamento de Psiquiatría, Sevilla, Spain.
- 23 Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom; Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, United Kingdom.
- 24 Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, South Africa; Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
- 25 Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
- 26 Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
- 27 Amsterdam Public Health Research Institute, Amsterdam UMC, Amsterdam, the Netherlands; Department of Biological Psychology, Faculty of Behavioral and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
- 28 School of Psychology and Counselling, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia.
- 29 Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom; Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, United Kingdom; Cardiff University's Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff, United Kingdom.
- 30 School of Psychology, University of Galway, Galway, Ireland; Center for Neuroimaging, Cognition and Genomics, University of Galway, Galway, Ireland.
- 31 Cardiff University's Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff, United Kingdom; Communicable Disease Surveillance Centre, Public Health Wales, Cardiff, Wales, United Kingdom.
- 32 Department of Psychology, University of Oslo, Oslo, Norway; Department of Psychology, Oslo New University College, Oslo, Norway.
- 33 Université Paris-Saclay, French Alternative Energies and Atomic Energy Commission, Neurospin, Gif-sur-Yvette, France.
- 34 Department of Psychological Science, University of Vermont, Burlington, Vermont.
- 35 Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
- 36 Department of Neurology, The University of Utah, Salt Lake City, Utah.
- 37 Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom.
- 38 Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
- 39 Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Centre for Research in Psychological Wellbeing, School of Psychology, University of Roehampton, London, United Kingdom.
- 40 Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois.
- 41 Department of Biomedicine, University of Bergen, Bergen, Norway; Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
- 42 Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway; MiDT National Research Center, Centre for Medical Equipment, Technology, and Innovation, St. Olav's Hospital, Trondheim, Norway.
- 43 Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Center for Mental Health, Partner Site Berlin-Potsdam, Berlin, Germany.
- 44 Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
- 45 Department of Biological Psychology, Faculty of Behavioral and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Neurological Disorder Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar.
- 46 Centre de recherche CHU Sainte Justine, Department of Psychiatry and Addictology, University of Montreal, Montreal, Quebec, Canada; Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada.
- 47 Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California.
- 48 Cardiff University's Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff, United Kingdom.
- 49 Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm & Stockholm Health Care Services, Stockholm Region, Stockholm, Sweden.
- 50 Biomedical Sciences of Cells and Systems, University Medical Center Groningen, Rijksuniversiteit Groningen, Groningen, the Netherlands.
- 51 Centre de recherche CHU Sainte Justine, Department of Psychiatry and Addictology, University of Montreal, Montreal, Quebec, Canada.
- 52 NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway; Dr. Einar Martens Research Group for Biological Psychiatry, Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
- 53 Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, Centre National de la Recherche Scientifique UMR 5293, Université de Bordeaux, Centre Broca Nouvelle-Aquitaine, Bordeaux, France.
- 54 Tri-institutional Center for Translational Research in Neuroimaging and Data Science, Georgia State, Georgia Tech, Emory University, Atlanta, Georgia; Department of Computer Science, Georgia State University, Atlanta, Georgia.
- 55 Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
- 56 Institut National de la Santé et de la Recherche Médicale (INSERM) U1299 "Trajectoires développementales et psychiatrie" Université Paris-Saclay, Centre National de la Recherche Scientifique, Centre Borelli, Gif-sur-Yvette, France.
- 57 Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia; Neuroscience Research Australia, Sydney, New South Wales, Australia.
- 58 Department of Pediatrics, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; Division of Human Genetics, 22q and You Center, Clinical Genetics Center, Section of Genetic Counseling, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Human Biology and Medical Genetics, Sapienza University, Rome, Italy.
- 59 School of Clinical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.
- 60 Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
- 61 Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
- 62 Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland.
- 63 Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig-Holstein, Kiel University, Kiel, Germany.
- 64 Institut National de la Santé et de la Recherche Médicale (INSERM) U1299 "Trajectoires développementales et psychiatrie" Université Paris-Saclay, Centre National de la Recherche Scientifique, Centre Borelli, Gif-sur-Yvette, France; Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Child and Adolescent Psychiatry Department, Pitié-salpêtrière Hospital, Paris, France.
- 65 Departments of Psychiatry and Neuroscience, Faculty of Medicine and Centre Hospitalier, Universitaire Sainte-Justine, University of Montreal, Montreal, Quebec, Canada; Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
- 66 Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
- 67 Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, Imperial College London, London, United Kingdom.
- 68 Neurodevelopment and Psychosis Section, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania.
- 69 Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, New South Wales, Australia.
- 70 Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, Western Cape, South Africa; Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa.
- 71 Neurodevelopment and Psychosis Section, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Neuroradiology, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.
- 72 Centre for Population Neuroscience and Stratified Medicine, Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, Shanghai, China; Centre for Population Neuroscience and Stratified Medicine, Department of Psychiatry and Clinical Neuroscience, Charite University Medicine, Berlin, Germany.
- 73 South African Medical Research Council Unit on Risk and Resilience, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
- 74 Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany; German Centre for Cardiovascular Research, Partner Site Greifswald, Greifswald, Germany.
- 75 Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia.
- 76 Instituto de Física de Cantabria, Santander, Spain; Department of Radiology, Instituto de Investigación Valdecilla, Marqués de Valdecilla University Hospital, Santander, Spain.
- 77 Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia; National Centre of Excellence in Intellectual Disability Health, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia.
- 78 Department of Child and Adolescent Psychiatry and Psychotherapy, TU Dresden, Dresden, Germany.
- 79 Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California; Department of Psychiatry, Charles R. Drew University of Medicine and Science, Los Angeles, California.
- 80 School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands.
- 81 School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands; Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
- 82 Centro de Investigación Biomédica en Red en Salud Mental, Sevilla, Spain; Department of Psychiatry, Instituto de Investigación Valdecilla, University Hospital Marqués de Valdecilla, Santander, Spain; Departamento de Medicina y Psiquiatría, Universidad de Cantabria, Santander, Spain.
- 83 German Centre for Cardiovascular Research, Partner Site Greifswald, Greifswald, Germany; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
- 84 Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
- 85 Department of Psychiatry, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; Genetics and Genome Biology, SickKids Research Institute, Toronto, Ontario, Canada.
- 86 Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
- 87 Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
- 88 Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Section for Precision Psychiatry, Oslo University Hospital, Oslo, Norway.
- 89 School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands. Electronic address: david.linden@maastrichtuniversity.nl.
- PMID: 40414598
- DOI: 10.1016/j.bpsc.2025.05.010
Item in Clipboard
Penetrance of Neurodevelopmental Copy Number Variants Is Associated With Variations in Cortical Morphology
Ana I Silva et al.
Biol Psychiatry Cogn Neurosci Neuroimaging.
.
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Format
doi: 10.1016/j.bpsc.2025.05.010.
Online ahead of print.
Authors
Ana I Silva
1
, Ida E Sønderby
2
, George Kirov
3
, Abdel Abdellaoui
4
, Ingrid Agartz
5
, David Ames
6
, Nicola J Armstrong
7
, Eric Artiges
8
, Tobias Banaschewski
9
, Anne S Bassett
10
, Carrie E Bearden
11
, John Blangero
12
, Rune Boen
13
, Dorret I Boomsma
14
, Robin Bülow
15
, Nancy J Butcher
16
, Vince Calhoun
17
, Linda E Campbell
18
, Eva W C Chow
19
, Simone Ciufolini
20
, Michael C Craig
21
, Benedicto Crespo-Farroco
22
, Adam C Cunningham
23
, Shareefa Dalvie
24
, Eileen Daly
25
, Paola Dazzan
26
, Eco J C de Geus
27
, Greig I de Zubicaray
28
, Joanne L Doherty
29
, Gary Donohoe
30
, Mark Drakesmith
31
, Thomas Espeseth
32
, Vincent Frouin
33
, Hugh Garavan
34
, David C Glahn
35
, Naomi J Goodrich-Hunsaker
36
, Penny A Gowland
37
, Hans J Grabe
38
, Antoine Grigis
33
, Maria Gudbrandsen
39
, Boris A Gutman
40
, Jan Haavik
41
, Asta K Håberg
42
, Jeremy Hall
3
, Andreas Heinz
43
, Sarah Hohmann
44
, Jouke-Jan Hottenga
45
, Sébastien Jacquemont
46
, Neda Jahanshad
47
, Rachel K Jonas
13
, Derek K Jones
48
, Erik G Jönsson
49
, Sanne Koops
50
, Kuldeep Kumar
51
, Stephanie Le Hellard
52
, Herve Lemaitre
53
, Jingyu Liu
54
, Astri J Lundervold
55
, Jean-Luc Martinot
56
, Karen A Mather
57
, Donna M McDonald-McGinn
58
, Katie L McMahon
59
, Allan F McRae
60
, Sarah E Medland
61
, Clara A Moreau
51
, Kieran C Murphy
62
, Declan Murphy
25
, Robin M Murray
20
, Frauke Nees
63
, Michael J Owen
3
, Marie-Laure Paillère Martinot
64
, Diimitri Papadopoulos Orfanos
33
, Tomas Paus
65
, Luise Poustka
66
, Tiago Reis Marques
67
, David R Roalf
68
, Perminder S Sachdev
69
, Freda Scheffler
70
, J Eric Schmitt
71
, Gunter Schumann
72
, Vidar M Steen
52
, Dan J Stein
73
, Lachlan T Strike
61
, Alexander Teumer
74
, Anbupalam Thalamuthu
75
, Sophia I Thomopoulos
47
, Diana Tordesillas-Gutiérrez
76
, Julian N Trollor
77
, Anne Uhlmann
78
, Ariana Vajdi
79
, Dennis van 't Ent
27
, Therese van Amelsvoort
80
, Marianne B M van den Bree
3
, Dennis van der Meer
81
, Javier Vázquez-Bourgon
82
, Julio E Villalón-Reina
47
, Uwe Völker
83
, Henry Völzke
84
, Jacob A S Vorstman
85
, Lars T Westlye
86
, Nigel Williams
23
, Katharina Wittfeld
38
, Margaret J Wright
87
, Paul M Thompson
47
, Ole A Andreassen
88
, David E J Linden
89
; ENIGMA-CNV Working Group
Affiliations
- 1 School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands; Neuroscience and Mental Health Innovation Institute, Cardiff University, Cardiff, United Kingdom; Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota. Electronic address: silvaai@umn.edu.
- 2 Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
- 3 Neuroscience and Mental Health Innovation Institute, Cardiff University, Cardiff, United Kingdom; Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom; Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, United Kingdom.
- 4 Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
- 5 Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm & Stockholm Health Care Services, Stockholm Region, Stockholm, Sweden; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
- 6 University of Melbourne Academic Unit for Psychiatry of Old Age, Kew, Victoria, Australia.
- 7 Mathematics and Statistics, Curtin University, Perth, Western Australia, Australia.
- 8 Institut National de la Santé et de la Recherche Médicale (INSERM) U1299 "Trajectoires développementales et psychiatrie" Université Paris-Saclay, Centre National de la Recherche Scientifique, Centre Borelli, Gif-sur-Yvette, France; Psychiatry Department, Établissement public de santé Barthélémy Durand, Étampes, Île-de-France, France.
- 9 Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
- 10 Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Dalglish Family 22q Clinic for Adults with 22q11.2 Deletion Syndrome, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
- 11 Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California; Department of Psychology, University of California, Los Angeles, California.
- 12 Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, Texas.
- 13 Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California.
- 14 Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Public Health Research Institute, Amsterdam UMC, Amsterdam, the Netherlands.
- 15 Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
- 16 Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
- 17 Tri-institutional Center for Translational Research in Neuroimaging and Data Science, Georgia State, Georgia Tech, Emory University, Atlanta, Georgia.
- 18 School of Psychological Science, University of Newcastle, Newcastle, New South Wales, Australia.
- 19 Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
- 20 Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
- 21 National Female Hormone Clinic, London, United Kingdom; Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
- 22 Centro de Investigación Biomédica en Red en Salud Mental, Sevilla, Spain; Instituto de Investigación Biomédica de Sevilla IBIS-CSIC, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Departamento de Psiquiatría, Sevilla, Spain.
- 23 Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom; Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, United Kingdom.
- 24 Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, South Africa; Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
- 25 Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
- 26 Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
- 27 Amsterdam Public Health Research Institute, Amsterdam UMC, Amsterdam, the Netherlands; Department of Biological Psychology, Faculty of Behavioral and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
- 28 School of Psychology and Counselling, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia.
- 29 Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom; Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, United Kingdom; Cardiff University's Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff, United Kingdom.
- 30 School of Psychology, University of Galway, Galway, Ireland; Center for Neuroimaging, Cognition and Genomics, University of Galway, Galway, Ireland.
- 31 Cardiff University's Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff, United Kingdom; Communicable Disease Surveillance Centre, Public Health Wales, Cardiff, Wales, United Kingdom.
- 32 Department of Psychology, University of Oslo, Oslo, Norway; Department of Psychology, Oslo New University College, Oslo, Norway.
- 33 Université Paris-Saclay, French Alternative Energies and Atomic Energy Commission, Neurospin, Gif-sur-Yvette, France.
- 34 Department of Psychological Science, University of Vermont, Burlington, Vermont.
- 35 Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
- 36 Department of Neurology, The University of Utah, Salt Lake City, Utah.
- 37 Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom.
- 38 Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
- 39 Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Centre for Research in Psychological Wellbeing, School of Psychology, University of Roehampton, London, United Kingdom.
- 40 Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois.
- 41 Department of Biomedicine, University of Bergen, Bergen, Norway; Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
- 42 Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway; MiDT National Research Center, Centre for Medical Equipment, Technology, and Innovation, St. Olav's Hospital, Trondheim, Norway.
- 43 Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Center for Mental Health, Partner Site Berlin-Potsdam, Berlin, Germany.
- 44 Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
- 45 Department of Biological Psychology, Faculty of Behavioral and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Neurological Disorder Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar.
- 46 Centre de recherche CHU Sainte Justine, Department of Psychiatry and Addictology, University of Montreal, Montreal, Quebec, Canada; Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada.
- 47 Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California.
- 48 Cardiff University's Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff, United Kingdom.
- 49 Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm & Stockholm Health Care Services, Stockholm Region, Stockholm, Sweden.
- 50 Biomedical Sciences of Cells and Systems, University Medical Center Groningen, Rijksuniversiteit Groningen, Groningen, the Netherlands.
- 51 Centre de recherche CHU Sainte Justine, Department of Psychiatry and Addictology, University of Montreal, Montreal, Quebec, Canada.
- 52 NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway; Dr. Einar Martens Research Group for Biological Psychiatry, Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
- 53 Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, Centre National de la Recherche Scientifique UMR 5293, Université de Bordeaux, Centre Broca Nouvelle-Aquitaine, Bordeaux, France.
- 54 Tri-institutional Center for Translational Research in Neuroimaging and Data Science, Georgia State, Georgia Tech, Emory University, Atlanta, Georgia; Department of Computer Science, Georgia State University, Atlanta, Georgia.
- 55 Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
- 56 Institut National de la Santé et de la Recherche Médicale (INSERM) U1299 "Trajectoires développementales et psychiatrie" Université Paris-Saclay, Centre National de la Recherche Scientifique, Centre Borelli, Gif-sur-Yvette, France.
- 57 Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia; Neuroscience Research Australia, Sydney, New South Wales, Australia.
- 58 Department of Pediatrics, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; Division of Human Genetics, 22q and You Center, Clinical Genetics Center, Section of Genetic Counseling, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Human Biology and Medical Genetics, Sapienza University, Rome, Italy.
- 59 School of Clinical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.
- 60 Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
- 61 Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
- 62 Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland.
- 63 Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig-Holstein, Kiel University, Kiel, Germany.
- 64 Institut National de la Santé et de la Recherche Médicale (INSERM) U1299 "Trajectoires développementales et psychiatrie" Université Paris-Saclay, Centre National de la Recherche Scientifique, Centre Borelli, Gif-sur-Yvette, France; Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Child and Adolescent Psychiatry Department, Pitié-salpêtrière Hospital, Paris, France.
- 65 Departments of Psychiatry and Neuroscience, Faculty of Medicine and Centre Hospitalier, Universitaire Sainte-Justine, University of Montreal, Montreal, Quebec, Canada; Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
- 66 Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
- 67 Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, Imperial College London, London, United Kingdom.
- 68 Neurodevelopment and Psychosis Section, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania.
- 69 Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, New South Wales, Australia.
- 70 Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, Western Cape, South Africa; Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa.
- 71 Neurodevelopment and Psychosis Section, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Neuroradiology, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.
- 72 Centre for Population Neuroscience and Stratified Medicine, Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, Shanghai, China; Centre for Population Neuroscience and Stratified Medicine, Department of Psychiatry and Clinical Neuroscience, Charite University Medicine, Berlin, Germany.
- 73 South African Medical Research Council Unit on Risk and Resilience, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
- 74 Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany; German Centre for Cardiovascular Research, Partner Site Greifswald, Greifswald, Germany.
- 75 Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia.
- 76 Instituto de Física de Cantabria, Santander, Spain; Department of Radiology, Instituto de Investigación Valdecilla, Marqués de Valdecilla University Hospital, Santander, Spain.
- 77 Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia; National Centre of Excellence in Intellectual Disability Health, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia.
- 78 Department of Child and Adolescent Psychiatry and Psychotherapy, TU Dresden, Dresden, Germany.
- 79 Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California; Department of Psychiatry, Charles R. Drew University of Medicine and Science, Los Angeles, California.
- 80 School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands.
- 81 School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands; Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
- 82 Centro de Investigación Biomédica en Red en Salud Mental, Sevilla, Spain; Department of Psychiatry, Instituto de Investigación Valdecilla, University Hospital Marqués de Valdecilla, Santander, Spain; Departamento de Medicina y Psiquiatría, Universidad de Cantabria, Santander, Spain.
- 83 German Centre for Cardiovascular Research, Partner Site Greifswald, Greifswald, Germany; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
- 84 Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
- 85 Department of Psychiatry, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; Genetics and Genome Biology, SickKids Research Institute, Toronto, Ontario, Canada.
- 86 Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
- 87 Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
- 88 Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Section for Precision Psychiatry, Oslo University Hospital, Oslo, Norway.
- 89 School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands. Electronic address: david.linden@maastrichtuniversity.nl.
- PMID: 40414598
- DOI: 10.1016/j.bpsc.2025.05.010
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Abstract
Background: Copy number variants (CNVs) may increase the risk for neurodevelopmental conditions. The neurobiological mechanisms that link these high-risk genetic variants to clinical phenotypes are largely unknown. An important question is whether brain abnormalities in individuals who carry CNVs are associated with their degree of penetrance.
Methods: We investigated whether increased CNV penetrance for schizophrenia and other developmental disorders was associated with variations in cortical and subcortical morphology. We pooled T1-weighted brain magnetic resonance imaging and genetic data from 22 cohorts from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis)-CNV consortium. In the main analyses, we included 9268 individuals (aged 7-90 years, 54% female), from which we identified 398 carriers of 36 neurodevelopmental CNVs at 20 distinct loci. A secondary analysis was performed including additional neuroimaging data from the ENIGMA-22q consortium, including 274 carriers of the 22q11.2 deletion and 291 noncarriers. CNV penetrance was estimated through penetrance scores that were previously generated from large cohorts of patients and controls. These scores represent the probability risk of developing either schizophrenia or other developmental disorders (including developmental delay, autism spectrum disorder, and congenital malformations).
Results: For both schizophrenia and developmental disorders, increased penetrance scores were associated with lower surface area in the cerebral cortex and lower intracranial volume. For both conditions, associations between CNV-penetrance scores and cortical surface area were strongest in regions of the occipital lobes, specifically in the cuneus and lingual gyrus.
Conclusions: Our findings link global and regional cortical morphometric features with CNV penetrance, providing new insights into neurobiological mechanisms of genetic risk for schizophrenia and other developmental disorders.
Keywords: Autism; Neuroimaging; Psychiatric disorders; Schizophrenia; Structural imaging.
Copyright © 2025 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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