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Sex differences in schizophrenia across the caudate nucleus, DLPFC, and hippocampus

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LIBD Sex Differences in Schizophrenia

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.

Citation

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.

Supplementary Data

We have uploaded the supplementary data to Zenodo.

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Sex differences in schizophrenia across the caudate nucleus, DLPFC, and hippocampus

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