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Penetrance of neurodevelopmental copy number variants is associated with variations in cortical morphology

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 a...

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Hauptverfasser: Silva, Ana I. (VerfasserIn) , Sønderby, Ida E. (VerfasserIn) , Kirov, George (VerfasserIn) , Abdellaoui, Abdel (VerfasserIn) , Agartz, Ingrid (VerfasserIn) , Ames, David (VerfasserIn) , Armstrong, Nicola J. (VerfasserIn) , Artiges, Eric (VerfasserIn) , Banaschewski, Tobias (VerfasserIn) , Bassett, Anne S. (VerfasserIn) , Bearden, Carrie E. (VerfasserIn) , Blangero, John (VerfasserIn) , Boen, Rune (VerfasserIn) , Boomsma, Dorret I. (VerfasserIn) , Bülow, Robin (VerfasserIn) , Butcher, Nancy J. (VerfasserIn) , Calhoun, Vince (VerfasserIn) , Campbell, Linda E. (VerfasserIn) , Chow, Eva W. C. (VerfasserIn) , Ciufolini, Simone (VerfasserIn) , Craig, Michael C. (VerfasserIn) , Crespo-Farroco, Benedicto (VerfasserIn) , Cunningham, Adam C. (VerfasserIn) , Dalvie, Shareefa (VerfasserIn) , Daly, Eileen (VerfasserIn) , Dazzan, Paola (VerfasserIn) , de Geus, Eco J. C. (VerfasserIn) , de Zubicaray, Greig I. (VerfasserIn) , Doherty, Joanne L. (VerfasserIn) , Donohoe, Gary (VerfasserIn) , Drakesmith, Mark (VerfasserIn) , Espeseth, Thomas (VerfasserIn) , Frouin, Vincent (VerfasserIn) , Garavan, Hugh (VerfasserIn) , Glahn, David C. (VerfasserIn) , Goodrich-Hunsaker, Naomi J. (VerfasserIn) , Gowland, Penny A. (VerfasserIn) , Grabe, Hans J. (VerfasserIn) , Grigis, Antoine (VerfasserIn) , Gudbrandsen, Maria (VerfasserIn) , Gutman, Boris A. (VerfasserIn) , Haavik, Jan (VerfasserIn) , Håberg, Asta K. (VerfasserIn) , Hall, Jeremy (VerfasserIn) , Heinz, Andreas (VerfasserIn) , Hohmann, Sarah (VerfasserIn) , Hottenga, Jouke-Jan (VerfasserIn) , Jacquemont, Sébastien (VerfasserIn) , Jahanshad, Neda (VerfasserIn) , Jonas, Rachel K. (VerfasserIn) , Jones, Derek K. (VerfasserIn) , Jönsson, Erik G. (VerfasserIn) , Koops, Sanne (VerfasserIn) , Kumar, Kuldeep (VerfasserIn) , Le Hellard, Stephanie (VerfasserIn) , Lemaitre, Herve (VerfasserIn) , Liu, Jingyu (VerfasserIn) , Lundervold, Astri J. (VerfasserIn) , Martinot, Jean-Luc (VerfasserIn) , Mather, Karen A. (VerfasserIn) , McDonald-McGinn, Donna M. (VerfasserIn) , McMahon, Katie L. (VerfasserIn) , McRae, Allan F. (VerfasserIn) , Medland, Sarah E. (VerfasserIn) , Moreau, Clara A. (VerfasserIn) , Murphy, Kieran C. (VerfasserIn) , Murphy, Declan (VerfasserIn) , Murray, Robin M. (VerfasserIn) , Nees, Frauke (VerfasserIn) , Owen, Michael J. (VerfasserIn) , Paillère Martinot, Marie-Laure (VerfasserIn) , Orfanos, Diimitri Papadopoulos (VerfasserIn) , Paus, Tomas (VerfasserIn) , Poustka, Luise (VerfasserIn) , Marques, Tiago Reis (VerfasserIn) , Roalf, David R. (VerfasserIn) , Sachdev, Perminder S. (VerfasserIn) , Scheffler, Freda (VerfasserIn) , Schmitt, J. Eric (VerfasserIn) , Schumann, Gunter (VerfasserIn) , Steen, Vidar M. (VerfasserIn) , Stein, Dan J. (VerfasserIn) , Strike, Lachlan T. (VerfasserIn) , Teumer, Alexander (VerfasserIn) , Thalamuthu, Anbupalam (VerfasserIn) , Thomopoulos, Sophia I. (VerfasserIn) , Tordesillas-Gutiérrez, Diana (VerfasserIn) , Trollor, Julian N. (VerfasserIn) , Uhlmann, Anne (VerfasserIn) , Vajdi, Ariana (VerfasserIn) , van ’t Ent, Dennis (VerfasserIn) , van Amelsvoort, Therese (VerfasserIn) , van den Bree, Marianne B. M. (VerfasserIn) , van der Meer, Dennis (VerfasserIn) , Vázquez-Bourgon, Javier (VerfasserIn) , Villalón-Reina, Julio E. (VerfasserIn) , Völker, Uwe (VerfasserIn) , Völzke, Henry (VerfasserIn) , Vorstman, Jacob A. S. (VerfasserIn) , Westlye, Lars T. (VerfasserIn) , Williams, Nigel (VerfasserIn) , Wittfeld, Katharina (VerfasserIn) , Wright, Margaret J. (VerfasserIn) , Thompson, Paul M. (VerfasserIn) , Andreassen, Ole A. (VerfasserIn) , Linden, David E. J. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: October 2025
In: Biological psychiatry. Cognitive neuroscience and neuroimaging
Year: 2025, Jahrgang: 10, Heft: 10, Pages: 1093-1106
ISSN:2451-9030
DOI:10.1016/j.bpsc.2025.05.010
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.bpsc.2025.05.010
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2451902225001697
Volltext
Verfasserangaben:Ana I. Silva, Ida E. Sønderby, George Kirov, Abdel Abdellaoui, Ingrid Agartz, David Ames, Nicola J. Armstrong, Eric Artiges, Tobias Banaschewski, Anne S. Bassett, Carrie E. Bearden, John Blangero, Rune Boen, Dorret I. Boomsma, Robin Bülow, Nancy J. Butcher, Vince Calhoun, Linda E. Campbell, Eva W. C. Chow, Simone Ciufolini, Michael C. Craig, Benedicto Crespo-Farroco, Adam C. Cunningham, Shareefa Dalvie, Eileen Daly, Paola Dazzan, Eco J. C. de Geus, Greig I. de Zubicaray, Joanne L. Doherty, Gary Donohoe, Mark Drakesmith, Thomas Espeseth, Vincent Frouin, Hugh Garavan, David C. Glahn, Naomi J. Goodrich-Hunsaker, Penny A. Gowland, Hans J. Grabe, Antoine Grigis, Maria Gudbrandsen, Boris A. Gutman, Jan Haavik, Asta K. Håberg, Jeremy Hall, Andreas Heinz, Sarah Hohmann, Jouke-Jan Hottenga, Sébastien Jacquemont, Neda Jahanshad, Rachel K. Jonas, Derek K. Jones, Erik G. Jönsson, Sanne Koops, Kuldeep Kumar, Stephanie Le Hellard, Herve Lemaitre, Jingyu Liu, Astri J. Lundervold, Jean-Luc Martinot, Karen A. Mather, Donna M. McDonald-McGinn, Katie L. McMahon, Allan F. McRae, Sarah E. Medland, Clara A. Moreau, Kieran C. Murphy, Declan Murphy, Robin M. Murray, Frauke Nees, Michael J. Owen, Marie-Laure Paillère Martinot, Diimitri Papadopoulos Orfanos, Tomas Paus, Luise Poustka, Tiago Reis Marques, David R. Roalf, Perminder S. Sachdev, Freda Scheffler, J. Eric Schmitt, Gunter Schumann, Vidar M. Steen, Dan J. Stein, Lachlan T. Strike, Alexander Teumer, Anbupalam Thalamuthu, Sophia I. Thomopoulos, Diana Tordesillas-Gutiérrez, Julian N. Trollor, Anne Uhlmann, Ariana Vajdi, Dennis van ’t Ent, Therese van Amelsvoort, Marianne B. M. van den Bree, Dennis van der Meer, Javier Vázquez-Bourgon, Julio E. Villalón-Reina, Uwe Völker, Henry Völzke, Jacob A. S. Vorstman, Lars T. Westlye, Nigel Williams, Katharina Wittfeld, Margaret J. Wright, Paul M. Thompson, Ole A. Andreassen, David E. J. Linden, for the ENIGMA-CNV Working Group

MARC

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245 1 0 |a Penetrance of neurodevelopmental copy number variants is associated with variations in cortical morphology  |c Ana I. Silva, Ida E. Sønderby, George Kirov, Abdel Abdellaoui, Ingrid Agartz, David Ames, Nicola J. Armstrong, Eric Artiges, Tobias Banaschewski, Anne S. Bassett, Carrie E. Bearden, John Blangero, Rune Boen, Dorret I. Boomsma, Robin Bülow, Nancy J. Butcher, Vince Calhoun, Linda E. Campbell, Eva W. C. Chow, Simone Ciufolini, Michael C. Craig, Benedicto Crespo-Farroco, Adam C. Cunningham, Shareefa Dalvie, Eileen Daly, Paola Dazzan, Eco J. C. de Geus, Greig I. de Zubicaray, Joanne L. Doherty, Gary Donohoe, Mark Drakesmith, Thomas Espeseth, Vincent Frouin, Hugh Garavan, David C. Glahn, Naomi J. Goodrich-Hunsaker, Penny A. Gowland, Hans J. Grabe, Antoine Grigis, Maria Gudbrandsen, Boris A. Gutman, Jan Haavik, Asta K. Håberg, Jeremy Hall, Andreas Heinz, Sarah Hohmann, Jouke-Jan Hottenga, Sébastien Jacquemont, Neda Jahanshad, Rachel K. Jonas, Derek K. Jones, Erik G. Jönsson, Sanne Koops, Kuldeep Kumar, Stephanie Le Hellard, Herve Lemaitre, Jingyu Liu, Astri J. Lundervold, Jean-Luc Martinot, Karen A. Mather, Donna M. McDonald-McGinn, Katie L. McMahon, Allan F. McRae, Sarah E. Medland, Clara A. Moreau, Kieran C. Murphy, Declan Murphy, Robin M. Murray, Frauke Nees, Michael J. Owen, Marie-Laure Paillère Martinot, Diimitri Papadopoulos Orfanos, Tomas Paus, Luise Poustka, Tiago Reis Marques, David R. Roalf, Perminder S. Sachdev, Freda Scheffler, J. Eric Schmitt, Gunter Schumann, Vidar M. Steen, Dan J. Stein, Lachlan T. Strike, Alexander Teumer, Anbupalam Thalamuthu, Sophia I. Thomopoulos, Diana Tordesillas-Gutiérrez, Julian N. Trollor, Anne Uhlmann, Ariana Vajdi, Dennis van ’t Ent, Therese van Amelsvoort, Marianne B. M. van den Bree, Dennis van der Meer, Javier Vázquez-Bourgon, Julio E. Villalón-Reina, Uwe Völker, Henry Völzke, Jacob A. S. Vorstman, Lars T. Westlye, Nigel Williams, Katharina Wittfeld, Margaret J. Wright, Paul M. Thompson, Ole A. Andreassen, David E. J. Linden, for the ENIGMA-CNV Working Group 
264 1 |c October 2025 
300 |b Illustrationen 
300 |a 14 
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337 |a Computermedien  |b c  |2 rdamedia 
338 |a Online-Ressource  |b cr  |2 rdacarrier 
500 |a Online verfügbar: 23. Mai 2025, Artikelversion: 6. Oktober 2025 
500 |a Gesehen am 05.02.2026 
520 |a 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. 
650 4 |a Autism 
650 4 |a Neuroimaging 
650 4 |a Psychiatric disorders 
650 4 |a Schizophrenia 
650 4 |a Structural imaging 
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700 1 |a Kirov, George  |e VerfasserIn  |4 aut 
700 1 |a Abdellaoui, Abdel  |e VerfasserIn  |4 aut 
700 1 |a Agartz, Ingrid  |e VerfasserIn  |4 aut 
700 1 |a Ames, David  |e VerfasserIn  |4 aut 
700 1 |a Armstrong, Nicola J.  |e VerfasserIn  |4 aut 
700 1 |a Artiges, Eric  |e VerfasserIn  |4 aut 
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700 1 |a Bearden, Carrie E.  |e VerfasserIn  |4 aut 
700 1 |a Blangero, John  |e VerfasserIn  |4 aut 
700 1 |a Boen, Rune  |e VerfasserIn  |4 aut 
700 1 |a Boomsma, Dorret I.  |e VerfasserIn  |4 aut 
700 1 |a Bülow, Robin  |e VerfasserIn  |4 aut 
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700 1 |a Calhoun, Vince  |e VerfasserIn  |4 aut 
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700 1 |a Ciufolini, Simone  |e VerfasserIn  |4 aut 
700 1 |a Craig, Michael C.  |e VerfasserIn  |4 aut 
700 1 |a Crespo-Farroco, Benedicto  |e VerfasserIn  |4 aut 
700 1 |a Cunningham, Adam C.  |e VerfasserIn  |4 aut 
700 1 |a Dalvie, Shareefa  |e VerfasserIn  |4 aut 
700 1 |a Daly, Eileen  |e VerfasserIn  |4 aut 
700 1 |a Dazzan, Paola  |e VerfasserIn  |4 aut 
700 1 |a de Geus, Eco J. C.  |e VerfasserIn  |4 aut 
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SER |a journal 
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SRT |a SILVAANAISPENETRANCE2025 

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