Cell type-specific coexpression networks funnel genetic risk into core genes

Cell type-specific immune gene coexpression hubs capture immune disease genetic risk, increasing genetically supported drug target success from 1.7-fold to 2.7-fold.

• Why it matters: Bulk and pseudobulk coexpression miss cell type-specific network structure, leaving unclear how genome-wide genetic risk maps onto core disease genes.
• What they did: Using population-scale single-cell immune transcriptomes, the study decomposed interindividual coexpression into cell type-shared versus cell type-specific networks and tested hub and edge enrichments with GWAS heritability, trans eQTLs, and perturb-seq.
• The result: Shared hubs were enriched for constrained housekeeping genes, while specific hubs were dynamically expressed and enriched for immune-matched enhancers, transcription factors, and immune disease GWAS signals, skewing edges toward upstream versus downstream disease-proximal genes.

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