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. 2025 Apr 15:55:e117.
doi: 10.1017/S0033291725000844.

Sleep and schizophrenia polygenic scores in non-affective and affective psychotic disorders

Erik Cederlöf  1   2   3 , Minna Holm  1 , Anders Kämpe  4 , Ari Ahola-Olli  4 , Katri Kantojärvi  1 , Markku Lähteenvuo  5 , Johan Ahti  2 , Jarmo Hietala  6 , Katja Häkkinen  5 , Erkki Isometsä  2 , Annamari Tuulio-Henriksson  7 , Olli Kampman  6   8   9   10   11 , Kaisla Lahdensuo  2 , Jouko Lönnqvist  1 , Jari Tiihonen  12 , Hannu Turunen  1 , Asko Wegelius  2 , Juha Veijola  7   13   14 , Tuula Kieseppä  15 , Aarno Palotie  4 , Tiina Paunio  1   2   3
Affiliations

Sleep and schizophrenia polygenic scores in non-affective and affective psychotic disorders

Erik Cederlöf et al. Psychol Med. .

Abstract

Background: Sleep problems are common in psychotic disorders and are associated with worse quality of life and disease prognosis. Genome-wide association studies (GWAS) have revealed genetic influences for schizophrenia and sleep, but polygenic scores (PGSs) for sleep traits have not been evaluated systematically in patients with psychotic disorders.

Methods: This study investigated the associations between PGSs for sleep traits (insomnia, PGSINS; sleep duration, PGSSD; short sleep duration, PGSSS; long sleep duration; PGSLS), diurnal preference (eveningness, PGSME), and schizophrenia (PGSSZ) with clinical features of psychotic disorders in the Finnish SUPER study comprising 8,232 patients with psychotic disorders. The measures included self-reported sleep and well-being, cognitive assessments, clozapine use, and functional outcomes. Using FinnGen data of 356,077 individuals, we analyzed the distributions of PGSs in psychotic and bipolar disorders and the general population.

Results: PGSINS associated with more sleep problems and worse well-being (e.g. worse health-related quality of life [β = -0.07, CI = -0.09, -0.05, p < .001]). High PGSSZ is associated with better sleep quality, worse clinical outcomes, and performance in cognitive tests (e.g. more errors in paired-associated learning [β = 0.07, CI = 0.04, 0.09, p < .001]). PGSINS was higher in affective psychotic and bipolar disorders, while PGSSD and PGSME were higher in schizophrenia as compared with individuals with no psychiatric disorders.

Conclusion: Genetic risks for sleep and diurnal preference vary between non-affective psychosis, affective psychosis, and the general population. The findings in this study emphasize the heterogeneity in genetic etiology of the objective features of disease severity and the more subjective measures related to well-being and self-reported measures of sleep.

Keywords: cognition; polygenic scores; psychotic disorders; schizophrenia; sleep.

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Conflict of interest statement

Regarding conflicts of interest, Markku Lähteenvuo is an owner and board member of Genomi Solutions Ltd. and Nursie Health Ltd. and has received honoraria from Sunovion, Orion Pharma, Janssen-Cilag, Otsuka Pharma, Lundbeck, and Medscape, travel funds from Sunovion, and research grants from the Finnish Medical Foundation, the Emil Aaltonen Foundation, and the Finnish Cultural Foundation. Jari Tiihonen has participated in research projects funded by grants from Janssen-Cilag and Eli Lilly to their employing institution; has received personal fees from the Finnish Medicines Agency (Fimea), European Medicines Agency (EMA), Eli Lilly, Janssen-Cilag, Lundbeck, and Otsuka; is a member of the advisory board for Lundbeck; and has received grants from the Stanley Foundation and the Sigrid Jusélius Foundation. Tiina Paunio has no COI related to the content of the current manuscript. Outside this work, she has received honoraria for lectures given at Idorsia Pharmaceuticals Ltd Masterclass 2023 and Biogen Workshop 2023. None of the other authors report any financial relationships with commercial interests.

Figures

Figure 1.
Figure 1.
Results from logistic and linear regression analyses for the polygenic scores. For congruency, the outcomes of subjective health, MHI-5, and EQ5D were inversed for this figure. Darker gray indicates positive coefficients (representing a worse outcome), while lighter gray indicates negative coefficients. * = significant after Bonferroni–Holm correction. All results significant before correction (p < 0.05) are colored. Note: PGSs in rows: INS, ‘insomnia’; SD, ‘sleep duration’; ME, ‘morning-eveningness (chronotype)’; SZ, ‘schizophrenia’; MHI-5, ‘Mental Health Inventory -5’; EQ5D, ‘Health-related quality of life’.
Figure 2.
Figure 2.
Boxplot showing the distribution of polygenic scores across different diagnostic groups.
See this image and copyright information in PMC

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