Sex affects transcriptional associations with schizophrenia across the dorsolateral prefrontal cortex, hippocampus, and caudate nucleus.
Nat Commun
; 15(1): 3980, 2024 May 10.
Article
in En
| MEDLINE
| ID: mdl-38730231
ABSTRACT
Schizophrenia is a complex neuropsychiatric disorder with sexually dimorphic features, including differential symptomatology, drug responsiveness, and male incidence rate. Prior large-scale transcriptome analyses for sex differences in schizophrenia have focused on the prefrontal cortex. Analyzing BrainSeq Consortium data (caudate nucleus n = 399, dorsolateral prefrontal cortex n = 377, and hippocampus n = 394), we identified 831 unique genes that exhibit sex differences across brain regions, enriched for immune-related pathways. We observed X-chromosome dosage reduction in the hippocampus of male individuals with schizophrenia. Our sex interaction model revealed 148 junctions dysregulated in a sex-specific manner in schizophrenia. Sex-specific schizophrenia analysis identified dozens of differentially expressed genes, notably enriched in immune-related pathways. Finally, our sex-interacting expression quantitative trait loci analysis revealed 704 unique genes, nine associated with schizophrenia risk. These findings emphasize the importance of sex-informed analysis of sexually dimorphic traits, inform personalized therapeutic strategies in schizophrenia, and highlight the need for increased female samples for schizophrenia analyses.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Schizophrenia
/
Caudate Nucleus
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Sex Characteristics
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Quantitative Trait Loci
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Dorsolateral Prefrontal Cortex
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Hippocampus
Limits:
Adult
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Female
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Humans
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Male
Language:
En
Journal:
Nat Commun
Year:
2024
Document type:
Article