Single-cell genetics identifies cell-type-specific effector genes across complex traits and diseases

Single-cell eQTL mapping in TenK10K phase 1 identifies cell-type-specific predicted effector genes across 69 diseases and 31 biomarker traits, spanning 54,245 and 348,103 associations.

• Why it matters: Bulk GWAS and eQTL analyses can obscure context-specific regulatory mechanisms, while sc-eQTL studies suggest genetic effects are often cell type- and subtype-specific.
• What they did: Using sc-eQTL results from 12,266 eGenes across 28 peripheral immune cell types, the study applies Mendelian randomisation and colocalisation to estimate directional effects at cell type resolution.
• The result: It quantifies polygenic enrichment to link distinct immune cell contributions to immune-related and systemic conditions, including differential enrichment of Crohn’s disease and COVID-19 in dendritic cell subtypes, and finds therapeutic compounds targeting identified gene-trait associations are twice as likely to secure regulatory approval.