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

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Autores de IDIVAL

Autores ajenos al IDIVAL

  • Silva AI
  • Sønderby IE
  • Kirov G
  • Abdellaoui A
  • Agartz I
  • Ames D
  • Armstrong NJ
  • Artiges E
  • Banaschewski T
  • Bassett AS
  • Bearden CE
  • Blangero J
  • Boen R
  • Boomsma DI
  • Bülow R
  • Butcher NJ
  • Calhoun V
  • Campbell LE
  • Chow EWC
  • Ciufolini S
  • Craig MC
  • Crespo-Farroco B
  • Cunningham AC
  • Dalvie S
  • Daly E
  • Dazzan P
  • de Geus EJC
  • de Zubicaray GI
  • Doherty JL
  • Donohoe G
  • Drakesmith M
  • Espeseth T
  • Frouin V
  • Garavan H
  • Glahn DC
  • Goodrich-Hunsaker NJ
  • Gowland PA
  • Grabe HJ
  • Grigis A
  • Gudbrandsen M
  • Gutman BA
  • Haavik J
  • Håberg AK
  • Hall J
  • Heinz A
  • Hohmann S
  • Hottenga JJ
  • Jacquemont S
  • Jahanshad N
  • Jonas RK
  • Jones DK
  • Jönsson EG
  • Koops S
  • Kumar K
  • Le Hellard S
  • Lemaitre H
  • Liu J
  • Lundervold AJ
  • Martinot JL
  • Mather KA
  • McDonald-McGinn DM
  • McMahon KL
  • McRae AF
  • Medland SE
  • Moreau CA
  • Murphy KC
  • Murphy D
  • Murray RM
  • Nees F
  • Owen MJ
  • Paillère Martinot ML
  • Orfanos DP
  • Paus T
  • Poustka L
  • Marques TR
  • Roalf DR
  • Sachdev PS
  • Scheffler F
  • Schmitt JE
  • Schumann G
  • Steen VM
  • Stein DJ
  • Strike LT
  • Teumer A
  • Thalamuthu A
  • Thomopoulos SI
  • Tordesillas-Gutiérrez D
  • Trollor JN
  • Uhlmann A
  • Vajdi A
  • Ent DV'
  • van Amelsvoort T
  • van den Bree MBM
  • van der Meer D
  • Villalón-Reina JE
  • Völker U
  • Völzke H
  • Vorstman JAS
  • Westlye LT
  • Williams N
  • Wittfeld K
  • Wright MJ
  • Thompson PM
  • Andreassen OA
  • Linden DEJ
  • ENIGMA-CNV working group

Unidades

Abstract

BACKGROUND: Copy number variants (CNVs) increase risk for neurodevelopmental conditions. The neurobiological mechanisms linking these high-risk genetic variants to clinical phenotypes are largely unknown. An important question is whether brain abnormalities in individuals carrying CNVs are associated with their degree of penetrance. METHODS: We investigated if 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-CNV consortium. In the main analyses, we included 9,268 individuals (aged 7 to 90 years, 54% females), 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 non-carriers. CNV-penetrance was estimated through penetrance scores that were previously generated from large cohorts of patients and controls. These scores represent the probability risk to develop 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.

Copyright © 2025. Published by Elsevier Inc.

Datos de la publicación

ISSN/ISSNe:
2451-9022, 2451-9030

Biological Psychiatry-Cognitive Neuroscience and Neuroimaging  ELSEVIER

Tipo:
Article
Páginas:
1093-1106
PubMed:
40414598

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Keywords

  • autism; neuroimaging; psychiatric disorders; schizophrenia; structural imaging

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