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Copy Number Variants increasing risk for schizophrenia: shared and distinct effects on brain morphometry and cognitive performance

Caseras, Xavier ORCID:, Legge, Sophie, Bracher-Smith, Matthew, Anney, Richard ORCID:, Owen, Michael ORCID:, Escott-Price, Valentina ORCID: and Kirov, George ORCID: 2022. Copy Number Variants increasing risk for schizophrenia: shared and distinct effects on brain morphometry and cognitive performance. Biological Psychiatry: Global Open Science 10.1016/j.bpsgos.2022.10.006
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Background 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 CNV and 202 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 modelling 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 (beta=-1.03, p=4x10-8; beta=-0.81, p=.00001) and performance in Digit Memory (beta=-1.58, p=.00003); while 1q21.1duplication did with volume on the putamen (beta=-0.70 p=.0004) and Reaction Time (beta=-1.14, p=.000002). We also showed that even when two 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.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Elsevier
ISSN: 2667-1743
Date of First Compliant Deposit: 25 October 2022
Date of Acceptance: 19 October 2022
Last Modified: 09 Feb 2023 13:50

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