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Copy Number Variants Increasing Risk for Schizophrenia: Shared and Distinct Effects on Brain Morphometry and Cognitive Performance

BACKGROUND: Copy number variations (CNVs) conferring risk for mental disorders are associated with brain changes and cognitive deficits. However, whether these effects are shared or distinct across CNVs remains untested. Here we compared the effects on brain morphometry and cognitive performance acr...

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Autores principales: Caseras, Xavier, Legge, Sophie E., Bracher-Smith, Matthew, Anney, Richard, Owen, Michael J., Escott-Price, Valentina, Kirov, George
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593876/
https://www.ncbi.nlm.nih.gov/pubmed/37881570
http://dx.doi.org/10.1016/j.bpsgos.2022.10.006
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author Caseras, Xavier
Legge, Sophie E.
Bracher-Smith, Matthew
Anney, Richard
Owen, Michael J.
Escott-Price, Valentina
Kirov, George
author_facet Caseras, Xavier
Legge, Sophie E.
Bracher-Smith, Matthew
Anney, Richard
Owen, Michael J.
Escott-Price, Valentina
Kirov, George
author_sort Caseras, Xavier
collection PubMed
description BACKGROUND: Copy number variations (CNVs) conferring risk for mental disorders are associated with brain changes and cognitive deficits. However, whether these effects are shared or distinct across CNVs remains untested. Here we compared the effects on brain morphometry and cognitive performance across CNVs with shared psychiatric liability. METHODS: Unaffected and unrelated participants of White British and Irish ancestry were drawn from the UK Biobank. After quality control, we retained 31,941 participants not carrying any damaging CNVs and 202 participants carrying one CNV increasing risk for schizophrenia. Using regression analyses, we tested the association between brain morphometry and cognitive performance with CNV carrying status and compared these effect sizes across CNVs using z test for the equality of regression coefficients. Equation modeling was used to examine the mediation of brain phenotypes on the association between CNVs and cognitive performance. RESULTS: We detected different patterns of association between CNVs and brain morphometry and cognitive abilities. Comparing across CNVs, 1q21.1 deletion showed the strongest association with surface area in frontal lobe (β = −1.03, p = 4 × 10(−8); β = −0.81, p = .00001) and performance in digit memory (β = −1.58, p = .00003), while 1q21.1 duplication showed the strongest association with volume of the putamen (β = −0.70, p = .0004) and reaction time (β = −1.14, p = .000002). We also showed that even when 2 CNVs were associated with performance in the same cognitive ability, these associations were mediated by different brain changes. CONCLUSIONS: Despite sharing similar psychiatric liability, the CNVs under study appeared to have different effects on brain morphometry and on performance in cognitive abilities, suggesting the existence of distinctive neurobiological pathways into the same clinical phenotypes.
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spelling pubmed-105938762023-10-25 Copy Number Variants Increasing Risk for Schizophrenia: Shared and Distinct Effects on Brain Morphometry and Cognitive Performance Caseras, Xavier Legge, Sophie E. Bracher-Smith, Matthew Anney, Richard Owen, Michael J. Escott-Price, Valentina Kirov, George Biol Psychiatry Glob Open Sci Archival Report BACKGROUND: Copy number variations (CNVs) conferring risk for mental disorders are associated with brain changes and cognitive deficits. However, whether these effects are shared or distinct across CNVs remains untested. Here we compared the effects on brain morphometry and cognitive performance across CNVs with shared psychiatric liability. METHODS: Unaffected and unrelated participants of White British and Irish ancestry were drawn from the UK Biobank. After quality control, we retained 31,941 participants not carrying any damaging CNVs and 202 participants carrying one CNV increasing risk for schizophrenia. Using regression analyses, we tested the association between brain morphometry and cognitive performance with CNV carrying status and compared these effect sizes across CNVs using z test for the equality of regression coefficients. Equation modeling was used to examine the mediation of brain phenotypes on the association between CNVs and cognitive performance. RESULTS: We detected different patterns of association between CNVs and brain morphometry and cognitive abilities. Comparing across CNVs, 1q21.1 deletion showed the strongest association with surface area in frontal lobe (β = −1.03, p = 4 × 10(−8); β = −0.81, p = .00001) and performance in digit memory (β = −1.58, p = .00003), while 1q21.1 duplication showed the strongest association with volume of the putamen (β = −0.70, p = .0004) and reaction time (β = −1.14, p = .000002). We also showed that even when 2 CNVs were associated with performance in the same cognitive ability, these associations were mediated by different brain changes. CONCLUSIONS: Despite sharing similar psychiatric liability, the CNVs under study appeared to have different effects on brain morphometry and on performance in cognitive abilities, suggesting the existence of distinctive neurobiological pathways into the same clinical phenotypes. Elsevier 2022-10-29 /pmc/articles/PMC10593876/ /pubmed/37881570 http://dx.doi.org/10.1016/j.bpsgos.2022.10.006 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Archival Report
Caseras, Xavier
Legge, Sophie E.
Bracher-Smith, Matthew
Anney, Richard
Owen, Michael J.
Escott-Price, Valentina
Kirov, George
Copy Number Variants Increasing Risk for Schizophrenia: Shared and Distinct Effects on Brain Morphometry and Cognitive Performance
title Copy Number Variants Increasing Risk for Schizophrenia: Shared and Distinct Effects on Brain Morphometry and Cognitive Performance
title_full Copy Number Variants Increasing Risk for Schizophrenia: Shared and Distinct Effects on Brain Morphometry and Cognitive Performance
title_fullStr Copy Number Variants Increasing Risk for Schizophrenia: Shared and Distinct Effects on Brain Morphometry and Cognitive Performance
title_full_unstemmed Copy Number Variants Increasing Risk for Schizophrenia: Shared and Distinct Effects on Brain Morphometry and Cognitive Performance
title_short Copy Number Variants Increasing Risk for Schizophrenia: Shared and Distinct Effects on Brain Morphometry and Cognitive Performance
title_sort copy number variants increasing risk for schizophrenia: shared and distinct effects on brain morphometry and cognitive performance
topic Archival Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593876/
https://www.ncbi.nlm.nih.gov/pubmed/37881570
http://dx.doi.org/10.1016/j.bpsgos.2022.10.006
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