Медицинская библиотека · Biological psychiatry. Cognitive neuroscience and neuroimaging · 2025

Penetrance of Neurodevelopmental Copy Number Variants Is Associated With Variations in Cortical Morphology.

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

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Аннотация

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.

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

Предметные рубрики MeSH

Humans DNA Copy Number Variations Female Child Adolescent Male Penetrance Adult Middle Aged Aged Schizophrenia Young Adult Magnetic Resonance Imaging Neurodevelopmental Disorders Aged, 80 and over Cerebral Cortex Developmental Disabilities Genetic Predisposition to Disease

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