A1 Refereed original research article in a scientific journal
Genetic contribution to disease-course severity and progression in the SUPER-Finland study, a cohort of 10,403 individuals with psychotic disorders
Authors: Kämpe Anders, Suvisaari Jaana, Lähteenvuo Markku, Singh Tarjinder, Ahola-Olli Ari, Urpa Lea, Haaki Willehard, Hietala Jarmo, Isometsä Erkki, Jukuri Tuomas, Kampman Olli, Kieseppä Tuula, Lahdensuo Kaisla, Lönnqvist Jouko, Männynsalo Teemu, Paunio Tiina, Niemi-Pynttäri Jussi, Suokas Kimmo, Tuulio-Henriksson Annamari, Veijola Juha, Wegelius Asko; SUPERFinland-Researchers, Daly Mark, Taylor Jacob, Kendler Kenneth S., Palotie Aarno, Pietiläinen Olli
Publisher: Springer Nature
Publication year: 2024
Journal: Molecular Psychiatry
Journal name in source: Molecular psychiatry
Journal acronym: Mol Psychiatry
Volume: 29
Issue: 9
First page : 2733
Last page: 2741
ISSN: 1359-4184
eISSN: 1476-5578
DOI: https://doi.org/10.1038/s41380-024-02516-6
Web address : https://www.nature.com/articles/s41380-024-02516-6
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/387509024
Genetic factors contribute to the susceptibility of psychotic disorders, but less is known how they affect psychotic disease-course development. Utilizing polygenic scores (PGSs) in combination with longitudinal healthcare data with decades of follow-up we investigated the contributing genetics to psychotic disease-course severity and diagnostic shifts in the SUPER-Finland study, encompassing 10 403 genotyped individuals with a psychotic disorder. To longitudinally track the study participants' past disease-course severity, we created a psychiatric hospitalization burden metric using the full-coverage and nation-wide Finnish in-hospital registry (data from 1969 and onwards). Using a hierarchical model, ranking the psychotic diagnoses according to clinical severity, we show that high schizophrenia PGS (SZ-PGS) was associated with progression from lower ranked psychotic disorders to schizophrenia (OR = 1.32 [1.23-1.43], p = 1.26e-12). This development manifested already at psychotic illness onset as a higher psychiatric hospitalization burden, the proxy for disease-course severity. In schizophrenia (n = 5 479), both a high SZ-PGS and a low educational attainment PGS (EA-PGS) were associated with increased psychiatric hospitalization burden (p = 1.00e-04 and p = 4.53e-10). The SZ-PGS and the EA-PGS associated with distinct patterns of hospital usage. In individuals with high SZ-PGS, the increased hospitalization burden was composed of longer individual hospital stays, while low EA-PGS associated with shorter but more frequent hospital visits. The negative effect of a low EA-PGS was found to be partly mediated via substance use disorder, a major risk factor for hospitalizations. In conclusion, we show that high SZ-PGS and low EA-PGS both impacted psychotic disease-course development negatively but resulted in different disease-course trajectories.
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