Effects of shared and non-shared schizophrenia and bipolar disorder alleles on cognition and educational attainment in the UK Biobank

Richards, Alexander L., Fenner, Eilidh, Clifton, Nicholas E., Cameron, Darren, Tume, Claire E., Bray, Nicholas J., Legge, Sophie E., Walters, James T.R., Holmans, Peter A., O’Donovan, Michael C. and Owen, Michael J. ORCID: https://orcid.org/0000-0003-4798-0862 2025. Effects of shared and non-shared schizophrenia and bipolar disorder alleles on cognition and educational attainment in the UK Biobank. Biological Society: Global Open Science , 100601. 10.1016/j.bpsgos.2025.100601

Full text not available from this repository.

Abstract

Background Cognitive impairment is typically more severe in schizophrenia (SZ) than bipolar disorder (BD). We explored the underlying genetics and biology of this difference and its relationship to educational attainment (EA) using Genomic Structural Equation Modelling (gSEM). Methods Shared and differentiating fractions of liability for SZ and BD were derived and tested for association with general intelligence (g, 93541 participants), fluid intelligence (FI, 160465 participants), and EA (354609 participants) in the UK Biobank. Liabilities were tested for enrichment in genes with high expression specificity (HES) for developmental stages, cell types, and functional categories. Results Shared liability was associated with poorer cognition but higher EA. The SZ differentiating fraction (SZdiff) was associated with poorer cognition and lower EA. Adjusting for cognition, the effects of SZdiff on EA were attenuated but significant. The differentiating fraction was enriched for HES genes for young adulthood (20-30 years), mid-adulthood (30-60 years), and dentate gyrus. Conclusions Shared liability for SZ and BD is enriched for alleles conferring risk to poorer cognitive function in the general population, but is associated with noncognitive traits that enhance EA. In contrast, SZdiff is enriched for alleles that confer risk to poorer EA through both cognitive and non-cognitive mechanisms, which has implications for interventions. The enrichment of the differentiating fraction for HES genes in early and mid-adulthood and in the dentate gyrus highlights developmental stages and cell types important for further research.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by-nc-nd/4.0/, Start Date: 2025-08-18
Publisher:	Elsevier
ISSN:	2667-1743
Date of Acceptance:	14 August 2025
Last Modified:	28 Aug 2025 11:30
URI:	https://orca.cardiff.ac.uk/id/eprint/180718

Actions (repository staff only)

Edit Item