Single-nucleus atlas of cell-type specific genetic regulation in the human brain.

Single-nucleus analysis reveals cell-type-specific genetic regulation of 14,258 genes in the human prefrontal cortex, uncovering novel disease-related targets.

• Why it matters: Understanding how genetic variants influence gene expression in specific brain cell types is crucial for deciphering the mechanisms underlying neuropsychiatric and neurodegenerative diseases, yet remains largely unexplored.
• What they did: The study analyzed 5.6 million nuclei from 1,384 diverse donors using multi-resolution approaches across major cell classes and subclasses to map genetic regulation and its variation.
• The result: Findings include identification of cell type-specific regulatory effects, dynamic regulation across development, and distal trans-regulation, providing new insights into disease mechanisms and potential therapeutic targets.