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[Preprint]. 2025 May 21:2025.05.20.25328039.
doi: 10.1101/2025.05.20.25328039.

Polygenic Scores for Schizophrenia and Educational Attainment Predict Global Functioning Across Psychiatric Hospitalization Among People with Schizophrenia

Evan J Giangrande  1   2   3 , Anders Kämpe  4   5 , Jaana Suvisaari  6 , Markku Lähteenvuo  4   7 , Emilia Vartiainen  4 , Karita Salo  4 , Olli Pietiläinen  3   8 , Aarno Palotie  3   4 , Jordan W Smoller  2   3 , Benjamin M Neale  1   3
Affiliations

Polygenic Scores for Schizophrenia and Educational Attainment Predict Global Functioning Across Psychiatric Hospitalization Among People with Schizophrenia

Evan J Giangrande et al. medRxiv. .

Abstract

Importance: Schizophrenia is characterized by heterogeneity in disease outcomes and course. The extent to which this heterogeneity is associated with genetic variation is unclear.

Objective: To investigate whether polygenic scores (PGS) for schizophrenia and educational attainment are associated with global functioning during inpatient psychiatric hospitalization among patients with schizophrenia.

Design setting and participants: Adults with schizophrenia were recruited nationwide for the SUPER-Finland Study between 2015 and 2018. Global functioning scores recorded during hospitalizations between 1994 and 2019 were extracted from a complete, longitudinal register. Data for the current genetic association study were analyzed between May 2024 and April 2025. We used linear mixed-effects models to examine associations among PGS and global functioning at admission and discharge, as well as functional change during hospitalization.

Exposures: Psychiatric hospitalization and PGS for schizophrenia and educational attainment.

Main outcomes and measures: Admission global functioning, discharge global functioning, and functional change during hospitalization.

Results: We analyzed 117,810 global functioning scores from 59,795 hospitalizations and 5991 participants (2733 [45.62%] female, median [IQR] age = 47 [20] years). Higher schizophrenia PGS predicted lower admission global functioning (𝛃 = -0.20; 95% CI, -0.40 to 0.00; P = .05) and discharge global functioning (𝛃 = -0.36; 95% CI,-0.56 to -0.17; P < .001), and less functional improvement (𝛃 = -0.31; 95% CI, -0.49 to -0.14; P < .001). Higher educational attainment PGS predicted greater functional improvement (𝛃 = 0.20; 95% CI, 0.03 to 0.37; P = .02) but worse admission global functioning (𝛃 = -0.23; 95% CI, -0.43 to -0.04; P = .02).

Conclusions and relevance: Higher genetic liability for schizophrenia is associated with worse global functioning across psychiatric hospitalization, including less functional improvement. Integrating PGS and clinically relevant, longitudinal disease outcomes may help parse heterogeneity in schizophrenia prognosis and course.

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Conflict of interest statement

Conflicts of Interest and Financial Disclosures Dr. Smoller is a member of the Scientific Advisory Board of Sensorium Therapeutics (with options), and has received grant support from Biogen, Inc. Dr. Neale is a member of the scientific advisory board at Deep Genomics.

Figures

Figure 1.
Figure 1.. Global Functioning Across 59,795 Psychiatric Hospitalizations
GF: global functioning. Delta GF = Discharge GF - Admission GF. Dashed vertical lines depict median GF scores.
Figure 2.
Figure 2.. Phenotypic Associations Among Global Functioning Scores and Deep Phenotypes
GF: global functioning. Change GF = Discharge GF adjusted for Admission GF. RTI: Reaction Time. PAL: Paired Associates Learning. 5 Years: these variables were calculated for psychiatric hospitalizations within the initial 5 years following a participant’s first admission (Supplement). RTI and PAL were assessed at study entry (between November 2015 and December 2018). Bars depict 95% CIs.
Figure 3.
Figure 3.. Schizophrenia and EA PGS Predict Global Functioning Across Hospitalization
PGS: polygenic score. GF: global functioning. Change GF: Discharge GF adjusted for Admission GF. Bars depict 95% CIs.
See this image and copyright information in PMC

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