Common genetic variants contribute to heritability of age at onset of schizophrenia.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
13 06 2023
13 06 2023
Historique:
received:
17
01
2023
accepted:
02
06
2023
revised:
23
05
2023
medline:
14
6
2023
pubmed:
13
6
2023
entrez:
12
6
2023
Statut:
epublish
Résumé
Schizophrenia (SCZ) is a complex disorder that typically arises in late adolescence or early adulthood. Age at onset (AAO) of SCZ is associated with long-term outcomes of the disease. We explored the genetic architecture of AAO with a genome-wide association study (GWAS), heritability, polygenic risk score (PRS), and copy number variant (CNV) analyses in 4 740 subjects of European ancestry. Although no genome-wide significant locus was identified, SNP-based heritability of AAO was estimated to be between 17 and 21%, indicating a moderate contribution of common variants. We also performed cross-trait PRS analyses with a set of mental disorders and identified a negative association between AAO and common variants for SCZ, childhood maltreatment and attention-deficit/hyperactivity disorder. We also investigated the role of copy number variants (CNVs) in AAO and found an association with the length and number of deletions (P-value = 0.03), whereas the presence of CNVs previously reported in SCZ was not associated with earlier onset. To our knowledge, this is the largest GWAS of AAO of SCZ to date in individuals from European ancestry, and the first study to determine the involvement of common variants in the heritability of AAO. Finally, we evidenced the role played by higher SCZ load in determining AAO but discarded the role of pathogenic CNVs. Altogether, these results shed light on the genetic architecture of AAO, which needs to be confirmed with larger studies.
Identifiants
pubmed: 37308478
doi: 10.1038/s41398-023-02508-0
pii: 10.1038/s41398-023-02508-0
pmc: PMC10261125
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
201Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. The Author(s).
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