Effect of polygenic scores on the relationship between psychosis and cognition

Lauren Varney; Krisztina Jedlovszky; Baihan Wang; Stephen Murtough; Marius Cotic; Alvin Richards-Belle; Noushin Saadullah Khani; Robin Lau; Rosemary Abidoph; Andrew McQuillin; Johan H. Thygesen; Matthias Weisbrod; Dan Rujescu; John Powell; Andrew M. McIntosh; Kuang Lin; Cathryn Lewis; Ina Giegling; Marta Di Forti; Maria J. Arranz; Neeltje E.M. van Haren; Wim Veling; Jim van Os; Claudia J.P. Simons; Marieke van der Pluijm; Lieuwe de Haan; Wiepke Cahn; Therese van Amelsvoort; Behrooz Z. Alizadeh; Stephan Bender; Benedicto Crespo-Facorro; Jeremy Hall; Conrad Iyegbe; Eugenia Kravariti; Stephen M. Lawrie; Ignacio Mata; Colm McDonald; Robin M. Murray; Diana Prata; Timothea Toulopoulou; Neeltje E.M. van Haren; Elvira Bramon

doi:10.1038/s41398-025-03666-z

Effect of polygenic scores on the relationship between psychosis and cognition

Lauren Varney^*
, Krisztina Jedlovszky
, Baihan Wang
, Stephen Murtough
, Marius Cotic
, Alvin Richards-Belle
, Noushin Saadullah Khani
, Robin Lau
, Rosemary Abidoph
, Andrew McQuillin
, Johan H. Thygesen
, Matthias Weisbrod
, Dan Rujescu
, John Powell
, Andrew M. McIntosh
, Kuang Lin
, Cathryn Lewis
, Ina Giegling
, Marta Di Forti
, Maria J. Arranz

Neeltje E.M. van Haren, Wim Veling, Jim van Os, Claudia J.P. Simons, Marieke van der Pluijm, Lieuwe de Haan, Wiepke Cahn, Therese van Amelsvoort, Behrooz Z. Alizadeh, Stephan Bender, Benedicto Crespo-Facorro, Jeremy Hall, Conrad Iyegbe, Eugenia Kravariti, Stephen M. Lawrie, Ignacio Mata, Colm McDonald, Robin M. Murray, Diana Prata, Timothea Toulopoulou, Neeltje E.M. van Haren, Elvira Bramon^*, ,

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

1 Downloads (Pure)

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.

Original language	English
Article number	491
Number of pages	12
Journal	Translational Psychiatry
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41398-025-03666-z
Publication status	Published - 21 Nov 2025

Access to Document

10.1038/s41398-025-03666-zLicence: CC BY

Effect of polygenic scores on the relationship between psychosis and cognitionFinal published version, 1.89 MBLicence: CC BY

Cite this

Varney, L., Jedlovszky, K., Wang, B., Murtough, S., Cotic, M., Richards-Belle, A., Saadullah Khani, N., Lau, R., Abidoph, R., McQuillin, A., Thygesen, J. H., Weisbrod, M., Rujescu, D., Powell, J., McIntosh, A. M., Lin, K., Lewis, C., Giegling, I., Di Forti, M. (2025). Effect of polygenic scores on the relationship between psychosis and cognition. Translational Psychiatry, 15(1), Article 491. https://doi.org/10.1038/s41398-025-03666-z

@article{7f1984f20a714a90a3c90001d310d613,

title = "Effect of polygenic scores on the relationship between psychosis and cognition",

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.",

author = "Lauren Varney and Krisztina Jedlovszky and Baihan Wang and Stephen Murtough and Marius Cotic and Alvin Richards-Belle and \{Saadullah Khani\}, Noushin and Robin Lau and Rosemary Abidoph and Andrew McQuillin and Thygesen, \{Johan H.\} and Matthias Weisbrod and Dan Rujescu and John Powell and McIntosh, \{Andrew M.\} and Kuang Lin and Cathryn Lewis and Ina Giegling and \{Di Forti\}, Marta and Arranz, \{Maria J.\} and \{van Haren\}, \{Neeltje E.M.\} and Wim Veling and \{van Os\}, Jim and Simons, \{Claudia J.P.\} and \{van der Pluijm\}, Marieke and \{de Haan\}, Lieuwe and Wiepke Cahn and \{van Amelsvoort\}, Therese and Alizadeh, \{Behrooz Z.\} and Stephan Bender and Benedicto Crespo-Facorro and Jeremy Hall and Conrad Iyegbe and Eugenia Kravariti and Lawrie, \{Stephen M.\} and Ignacio Mata and Colm McDonald and Murray, \{Robin M.\} and Diana Prata and Timothea Toulopoulou and \{van Haren\}, \{Neeltje E.M.\} and Elvira Bramon",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = nov,

day = "21",

doi = "10.1038/s41398-025-03666-z",

language = "English",

volume = "15",

journal = "Translational Psychiatry",

issn = "2158-3188",

publisher = "Springer Nature",

number = "1",

}

Varney, L, Jedlovszky, K, Wang, B, Murtough, S, Cotic, M, Richards-Belle, A, Saadullah Khani, N, Lau, R, Abidoph, R, McQuillin, A, Thygesen, JH, Weisbrod, M, Rujescu, D, Powell, J, McIntosh, AM, Lin, K, Lewis, C, Giegling, I, Di Forti, M, Arranz, MJ, van Haren, NEM, Veling, W, van Os, J, Simons, CJP, van der Pluijm, M, de Haan, L, Cahn, W, van Amelsvoort, T, Alizadeh, BZ, Bender, S, Crespo-Facorro, B, Hall, J, Iyegbe, C, Kravariti, E, Lawrie, SM, Mata, I, McDonald, C, Murray, RM, Prata, D, Toulopoulou, T, van Haren, NEM, Bramon, E 2025, 'Effect of polygenic scores on the relationship between psychosis and cognition', Translational Psychiatry, vol. 15, no. 1, 491. https://doi.org/10.1038/s41398-025-03666-z

TY - JOUR

T1 - Effect of polygenic scores on the relationship between psychosis and cognition

AU - Varney, Lauren

AU - Jedlovszky, Krisztina

AU - Wang, Baihan

AU - Murtough, Stephen

AU - Cotic, Marius

AU - Richards-Belle, Alvin

AU - Saadullah Khani, Noushin

AU - Lau, Robin

AU - Abidoph, Rosemary

AU - McQuillin, Andrew

AU - Thygesen, Johan H.

AU - Weisbrod, Matthias

AU - Rujescu, Dan

AU - Powell, John

AU - McIntosh, Andrew M.

AU - Lin, Kuang

AU - Lewis, Cathryn

AU - Giegling, Ina

AU - Di Forti, Marta

AU - Arranz, Maria J.

AU - van Haren, Neeltje E.M.

AU - Veling, Wim

AU - van Os, Jim

AU - Simons, Claudia J.P.

AU - van der Pluijm, Marieke

AU - de Haan, Lieuwe

AU - Cahn, Wiepke

AU - van Amelsvoort, Therese

AU - Alizadeh, Behrooz Z.

AU - Bender, Stephan

AU - Crespo-Facorro, Benedicto

AU - Hall, Jeremy

AU - Iyegbe, Conrad

AU - Kravariti, Eugenia

AU - Lawrie, Stephen M.

AU - Mata, Ignacio

AU - McDonald, Colm

AU - Murray, Robin M.

AU - Prata, Diana

AU - Toulopoulou, Timothea

AU - van Haren, Neeltje E.M.

AU - Bramon, Elvira

PY - 2025/11/21

Y1 - 2025/11/21

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105022670743

U2 - 10.1038/s41398-025-03666-z

DO - 10.1038/s41398-025-03666-z

M3 - Article

C2 - 41271631

AN - SCOPUS:105022670743

SN - 2158-3188

VL - 15

JO - Translational Psychiatry

JF - Translational Psychiatry

IS - 1

M1 - 491

ER -

Effect of polygenic scores on the relationship between psychosis and cognition

Abstract

Access to Document

Other files and links

Fingerprint

Cite this