Single-cell brain atlas maps gene regulation across 1,384 donors
Researchers built a single-nucleus atlas of genetic regulation in the human prefrontal cortex, drawing on 5.6 million nuclei from 1,384 donors of diverse ancestries. The study, published in Nature Genetics, identified regulatory effects for 14,258 genes across eight major cell classes and 27 subclasses, with 981 genes showing cell type-specific effects at the class level and 857 at the subclass level. By colocalizing regulatory variants with disease traits, the team found cell type-specific genes tied to Alzheimer's disease and schizophrenia that bulk analyses had missed. They also tracked 2,073 genes whose regulatory effects shift across developmental trajectories and found 1,655 genes with trans-regulatory effects controlling gene expression at a distance.
For patients with neuropsychiatric or neurodegenerative conditions, a map this detailed points researchers toward which cell types drive genetic risk, giving disease research sharper targets. Clinical treatments built on these findings do not yet exist.
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