Effect of polygenic scores on the relationship between psychosis and cognition

Varney, Lauren, Jedlovszky, Krisztina, Wang, Baihan, Murtough, Stephen, Cotic, Marius, Richards-Belle, Alvin, Saadullah Khani, Noushin, Lau, Robin, Abidoph, Rosemary, McQuillin, Andrew, Thygesen, Johan H., Alizadeh, Behrooz Z., Bender, Stephan, Crespo-Facorro, Benedicto, Hall, Jeremy ORCID: https://orcid.org/0000-0003-2737-9009, Iyegbe, Conrad, Kravariti, Eugenia, Lawrie, Stephen M., Mata, Ignacio, McDonald, Colm, Murray, Robin M., Prata, Diana, Toulopoulou, Timothea, van Haren, Neeltje EM and Bramon, Elvira 2025. Effect of polygenic scores on the relationship between psychosis and cognition. Translational Psychiatry 15 (1) , 491. 10.1038/s41398-025-03666-z

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Abstract

Cognitive impairment is an important but often under-researched symptom in psychosis. Both psychosis and cognition are highly heritable and there is evidence of a genetic effect on the relationship between them. Using samples of adults (N = 4 506) and children (N = 10 981), we investigated the effect of schizophrenia and bipolar disorder polygenic scores on cognitive performance, and intelligence and educational attainment polygenic scores on psychosis presentation. Schizophrenia polygenic score was negatively associated with visuospatial processing in adults (beta: −0.0569; 95% confidence interval [CI]: −0.0926, −0.0212) and working memory (beta: −0.0432; 95% CI: −0.0697, −0.0168), processing speed (beta: −0.0491; 95% CI: −0.0760, −0.0223), episodic memory (betas: −0.0581 to −0.0430; 95% CIs: −0.0847, −0.0162), executive functioning (beta: −0.0423; 95% CI: −0.0692, −0.0155), fluid intelligence (beta: −0.0583; 95% CI: −0.0847, −0.0320), and total intelligence (beta: −0.0458; 95% CI: −0.0709, −0.0206) in children. Bipolar disorder polygenic score was not associated with any cognitive domains studied. Lower polygenic scores for intelligence were associated with greater odds of psychosis in adults (odds ratio [OR]: 0.886; 95% CI: 0.811–0.968). In children, lower polygenic scores for both intelligence (OR: 0.829; 95% CI: 0.777–0.884) and educational attainment (OR: 0.771; 95% CI: 0.724–0.821) were associated with greater odds of psychotic-like experiences. Our findings suggest that polygenic scores for both cognitive phenotypes and psychosis phenotypes are implicated in the relationship between psychosis and cognitive performance. Further research is needed to determine the direction of this effect and the mechanisms by which it occurs.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Schools > Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	Springer Nature [academic journals on nature.com]
Date of First Compliant Deposit:	26 November 2025
Date of Acceptance:	2 October 2025
Last Modified:	26 Nov 2025 10:30
URI:	https://orca.cardiff.ac.uk/id/eprint/182676

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