Sex and autism share cell type-specific effects on cortical gene expression

Sex-linked gene expression differences across six cortical regions show stronger overlap with autism-related frontal cortex signatures than with schizophrenia, with a shared transcriptomic axis.

• Why it matters: Bulk-tissue analyses may miss cell type heterogeneity, leaving unclear whether sex effects on brain gene expression align with autism neurobiology beyond schizophrenia.
• What they did: Using single-nucleus RNA-seq, the study estimated sex effects across six cortical regions (169 samples, 30 individuals) and autism effects in frontal cortex (63 individuals, 33 cases), comparing to schizophrenia (140 individuals, 65 cases).
• The result: Genes with significant sex effects overlapped more with autism than schizophrenia, and multivariate analysis identified a shared sex–autism axis enriched for autism risk genes and synaptic biology, with cell type–specific directionality.

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