Single-cell transcriptome-wide Mendelian randomization and colocalization analyses reveal immune-cell-specific mechanisms and actionable drug targets in prostate cancer

Integrating single-cell cis-eQTLs across 14 immune cell types with prostate cancer GWAS prioritized 80 eGene–cell-type associations, especially in CD4+ and CD8+ T-cell subsets.

• Why it matters: Immune-targeted therapies have limited success in prostate cancer, and the field lacks immune-cell-resolved genetically prioritized targets tied to susceptibility signals.
• What they did: The study combined Mendelian randomization and Bayesian colocalization using PRACTICAL and FinnGen GWAS, bulk eQTLs, and single-cell RNA-seq from prostate tumors, then meta-analyzed 52 nominally significant eGene–cell-type associations across 25 genes.
• The result: Prioritized genes were mapped across immune populations in the prostate tumor microenvironment, including HLA-DQA2, TXN, and COX6B1, and drug-target links highlighted candidates such as IGF1R and FAAH for further investigation.