Reported race-associated differences in control and schizophrenia post-mortem brain transcriptomes implicate...

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Racial disparities in schizophrenia (SCZ) illness courses and outcomes are not well understood.
• Social gradients are implicated, but their neuro-molecular correlates remain unclear.
• Brain differences underlying disparate psychiatric outcomes require further investigation.

Purpose of the Study:

• To investigate neuro-molecular differences in the brain related to race and SCZ.
• To analyze gene expression patterns in dorsolateral prefrontal cortex (DLPFC) across diverse cohorts.
• To identify molecular correlates of social gradients and their overlap with SCZ.

Main Methods:

• Analyzed post-mortem DLPFC RNAseq data from two racially diverse cohorts (CommonMind Consortium).
• Utilized differential gene expression and gene set variation analyses.
• Included 322 SCZ cases and 459 controls, with reported race data.

Main Results:

• Identified 1,514 differentially expressed genes between reported race groups, consistent across cohorts.
• Functional enrichment revealed upregulation of stress and immune response genes.
• Found 109 significant gene sets implicating metabolic and immune pathways in race-dependent SCZ associations.

Conclusions:

• Discovered molecular mechanisms uniquely perturbed across reported race groups in SCZ.
• Identified candidate pathways associated with SCZ in a reported race-dependent manner.
• Emphasized the need for diverse cohort data to understand population-level SCZ pathogenesis.