Effect of polygenic scores on the relationship between psychosis and cognition
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.
Authors
- Conrad Osamede Iyegbe (ORCID: https://orcid.org/0000-0003-4908-5183)
- Andrew Mark McIntosh (ORCID: https://orcid.org/0000-0002-0198-4588)
- John Powell (ORCID: https://orcid.org/0000-0001-6124-439X)
- Jérémy Hall (ORCID: https://orcid.org/0000-0002-0403-3278)
- Diana Pinto Prata (ORCID: https://orcid.org/0000-0002-4051-022X)
- Lauren Varney (ORCID: https://orcid.org/0009-0009-1139-4790)
- Thérèse van Amelsvoort (ORCID: https://orcid.org/0000-0003-1135-5133)
- Jim van Os (ORCID: https://orcid.org/0000-0002-7245-1586)
- Robin M. Murray (ORCID: https://orcid.org/0000-0003-0829-0519)
- Benedicto Crespo‐Facorro (ORCID: https://orcid.org/0000-0003-0033-7132)
- Alvin Richards‐Belle (ORCID: https://orcid.org/0000-0001-8577-9380)
- Johan H. Thygesen (ORCID: https://orcid.org/0000-0002-7479-3459)
- Maria Jesús Arranz (ORCID: https://orcid.org/0000-0002-6757-9198)
- Eugenia Kravariti (ORCID: https://orcid.org/0000-0003-1119-0324)
- Ina Giegling (ORCID: https://orcid.org/0000-0001-8407-7512)
- Dan Rujescu (ORCID: https://orcid.org/0000-0002-1432-313X)
- Cathryn M. Lewis (ORCID: https://orcid.org/0000-0002-8249-8476)
- Stephan Bender (ORCID: https://orcid.org/0000-0001-8199-3785)
- Marieke van der Pluijm (ORCID: https://orcid.org/0000-0003-0665-7911)
- Neeltje E.M. van Haren (ORCID: https://orcid.org/0000-0002-3090-7653)
- Andrew McQuillin (ORCID: https://orcid.org/0000-0003-1567-2240)
- Stephen M. Lawrie (ORCID: https://orcid.org/0000-0002-2444-5675)
- Claudia J.P. Simons (ORCID: https://orcid.org/0000-0002-7637-3589)
- Baihan Wang (ORCID: https://orcid.org/0000-0001-6986-8236)
- Marius Cotic (ORCID: https://orcid.org/0000-0002-1481-9100)
- Matthias Weisbrod (ORCID: https://orcid.org/0000-0002-1760-480X)
- Colm McDonald (ORCID: https://orcid.org/0000-0003-1661-5192)
- Noushin Saadullah Khani (ORCID: https://orcid.org/0009-0004-6678-4693)
- Timothea Toulopoulou (ORCID: https://orcid.org/0000-0002-9062-8314)
- Wim Veling (ORCID: https://orcid.org/0000-0002-1364-9779)
- Rosemary Abidoph
- Elvira Bramon (ORCID: https://orcid.org/0000-0003-1369-5983)
- Behrooz Z. Alizadeh (ORCID: https://orcid.org/0000-0002-1415-8007)
- Robin Lau
- Marta Di Forti (ORCID: https://orcid.org/0000-0002-3218-6925)
- Kuang Lin (ORCID: https://orcid.org/0000-0003-3017-6026)
- Ignacio Fernández de Mata (ORCID: https://orcid.org/0000-0002-9511-0469)
- Krisztina Jedlovszky
- Stephen Murtough
- Lieuwe de Haan
- Wiepke Cahn
Institutions
- University Medical Center Groningen (NL)
- University of Lisbon (PT)
- Bilkent University (TR)
- University of Groningen (NL)
- King's College London (GB)
- Ollscoil na Gaillimhe – University of Galway (IE)
- National and Kapodistrian University of Athens (GR)
- Heidelberg University (DE)
- North East London NHS Foundation Trust (GB)
- Great Ormond Street Hospital (GB)
- University Medical Center Utrecht (NL)
- Maastricht University (NL)
- University of Oxford (GB)
- Fundación Caja Navarra (ES)
- Mount Sinai Hospital (US)
- Amsterdam Neuroscience (NL)
- Kings Health Partners (GB)
- Navarrabiomed (ES)
- Mútua Terrassa (ES)
- Instituto de Biomedicina de Sevilla (ES)
- Cognitive Neuroimaging Lab (FR)
- The London College (GB)
- Arkin (NL)
- Reinier van Arkel (NL)
- University Hospital Cologne (DE)
- Altrecht GGZ (NL)
- Clinical Science Institute (US)
- University College London (GB)
- Amsterdam University of Applied Sciences (NL)
- Medical University of Vienna (AT)
- Universidad de Sevilla (ES)
- Cardiff University (GB)
- University of Amsterdam (NL)
- Erasmus University Rotterdam (NL)
- University of Edinburgh (GB)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Translational Psychiatry
- Published
- 2025-11-21
- DOI
- https://doi.org/10.1038/s41398-025-03666-z
- Primary Topic
- Schizophrenia research and treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00