Sex affects transcriptional associations with schizophrenia across the dorsolateral prefrontal cortex, hippocampus, and caudate nucleus.

Autor:	Benjamin KJM; Lieber Institute for Brain Development, Baltimore, MD, USA. KynonJade.Benjamin@libd.org.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. KynonJade.Benjamin@libd.org.; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. KynonJade.Benjamin@libd.org., Arora R; Lieber Institute for Brain Development, Baltimore, MD, USA.; Department of Biology, Johns Hopkins University Krieger School of Arts & Sciences, Baltimore, MD, USA., Feltrin AS; Lieber Institute for Brain Development, Baltimore, MD, USA., Pertea G; Lieber Institute for Brain Development, Baltimore, MD, USA., Giles HH; Lieber Institute for Brain Development, Baltimore, MD, USA.; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Stolz JM; Lieber Institute for Brain Development, Baltimore, MD, USA., D'Ignazio L; Lieber Institute for Brain Development, Baltimore, MD, USA.; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Collado-Torres L; Lieber Institute for Brain Development, Baltimore, MD, USA.; Center for Computational Biology, Johns Hopkins University, Baltimore, MD, USA., Shin JH; Lieber Institute for Brain Development, Baltimore, MD, USA., Ulrich WS; Lieber Institute for Brain Development, Baltimore, MD, USA., Hyde TM; Lieber Institute for Brain Development, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Kleinman JE; Lieber Institute for Brain Development, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Weinberger DR; Lieber Institute for Brain Development, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Paquola ACM; Lieber Institute for Brain Development, Baltimore, MD, USA. Apua.Paquola@libd.org.; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Apua.Paquola@libd.org., Erwin JA; Lieber Institute for Brain Development, Baltimore, MD, USA. Jennifer.Erwin@libd.org.; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Jennifer.Erwin@libd.org.; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Jennifer.Erwin@libd.org.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2024 May 10; Vol. 15 (1), pp. 3980. Date of Electronic Publication: 2024 May 10.
DOI:	10.1038/s41467-024-48048-z
Abstrakt:	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. (© 2024. The Author(s).)
Databáze:	MEDLINE
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