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.
If you use anything in this repository please cite the following pre-print:
Kynon JM Benjamin*+, Ria Arora+, Arthur S Feltrin, Geo Pertea, Hunter Giles, Josh Stolz, Laura D’Ignazio, Leonardo Collado-Torres, Thomas M Hyde, Joel E Kleinman, Daniel R Weinberger, Apuã CM Paquola*, Jennifer Erwin*. Sex affects transcriptional associations with schizophrenia across dorsolateral prefrontal cortex, hippocampus, and caudate nucleus. Nature Communications. 2024.
*Corresponding authors
+Co-first authors
PMID: 38730231.
We have uploaded the supplementary data to Zenodo.
This license lets others remix, tweak, and build upon our work non-commercially as long as they acknowledge our work.