Varney, Lauren;
Jedlovszky, Krisztina;
Wang, Baihan;
Murtough, Stephen;
Cotic, Marius;
Richards-Belle, Alvin;
Saadullah Khani, Noushin;
... Bramon, Elvira; + view all
(2025)
Effect of polygenic scores on the relationship between psychosis and cognition.
Translational Psychiatry
, 15
, Article 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.
| Type: | Article |
|---|---|
| Title: | Effect of polygenic scores on the relationship between psychosis and cognition |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41398-025-03666-z |
| Publisher version: | https://doi.org/10.1038/s41398-025-03666-z |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Genetics, Predictive markers |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences > Institute of Cognitive Neuroscience UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry > Mental Health Neuroscience |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10217812 |
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