Single-cell profiling and genetic regulation of alternative polyadenylation in the human brain.

Single-cell APA profiling in the human brain reveals 3'aQTLs linked to 17 GWAS loci, including key genes for Alzheimer's, schizophrenia, and Parkinson's disease.

• Why it matters: Understanding gene regulation at cell type resolution is crucial for deciphering the genetic basis of brain diseases, yet APA regulation has remained largely uncharted in this context.
• What they did: The study generated a single-cell atlas of APA across 2 million cells from 379 postmortem brains, integrating APA variation with whole-genome sequencing to identify 3'aQTLs for 4,288 genes.
• The result: Findings show that 3'aQTLs often colocalize with pQTLs and are associated with disease loci, providing insights into cell-type-specific post-transcriptional regulation and its role in neurodegenerative and psychiatric disorders.