Genetic contribution to disease-course severity and progression in the SUPER-Finland study, a cohort of 10,403 individuals with psychotic disorders.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
01 Apr 2024
01 Apr 2024
Historique:
received:
21
07
2023
accepted:
04
03
2024
revised:
28
02
2024
medline:
1
4
2024
pubmed:
1
4
2024
entrez:
31
3
2024
Statut:
aheadofprint
Résumé
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.
Identifiants
pubmed: 38556557
doi: 10.1038/s41380-024-02516-6
pii: 10.1038/s41380-024-02516-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Svenska Sällskapet för Medicinsk Forskning (Swedish Society for Medical Research)
ID : PD20-0190
Investigateurs
Aija Kyttälä
(A)
Ari Ahola-Olli
(A)
Auli Toivola
(A)
Benjamin Neale
(B)
Huei-Yi Shen
(HY)
Imre Västrik
(I)
Jari Tiihonen
(J)
Jarmo Hietala
(J)
Jouko Lönnqvist
(J)
Juha Veijola
(J)
Kaisla Lahdensuo
(K)
Katja Häkkinen
(K)
Mark Daly
(M)
Minna Holm
(M)
Noora Ristiluoma
(N)
Risto Kajanne
(R)
Steven E Hyman
(SE)
Tarjinder Singh
(T)
Informations de copyright
© 2024. The Author(s).
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