What it is
The authors built a single-nucleus, multi-ancestry atlas of how genetic variants regulate gene expression in the human prefrontal cortex, from 5.6 million nuclei from 1,384 donors of diverse ancestries. Across eight major cell classes and 27 subclasses they identify genetic regulation for 14,258 genes, 981 of them with cell type-specific effects at the class level and 857 at the subclass level. They also find 2,073 genes whose regulatory effects vary across developmental trajectories and 1,655 genes with trans-regulatory effects.
Why it matters
Genetic risk variants for common diseases sit predominantly in non-coding regulatory regions and act by changing gene expression, but the cellular specificity of those effects has remained largely unexplored. Colocalizing variants that regulate genes with variants associated with disease uncovers novel cell type-specific genes implicated in Alzheimer's disease, schizophrenia and other disorders that bulk tissue analyses could not detect.
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Filed underGenetic Associations and Epidemiology, Single-cell and spatial transcriptomics, Functional Brain Connectivity Studies