Genetic landscape and functional exploration of kidney cancer predisposition causality in cross-ancestral populations [screen]

To functionally explore renal cell carcinoma (RCC) susceptibility variants, we performed CUT&Tag for H3K27ac and ATAC-seq on 769P cells to assess transcriptional activity. Subsequently, we conducted a CRISPR screen and CRISPR droplet sequencing (CROP-seq), which combines pooled CRISPR screens with single-cell RNA sequencing (scRNA-seq), to identify target genes potentially regulated by likely causal SNPs. Functionally, we established a novel association between rs28684409 and the oncogene RPL4 at the complex genetic locus 15q22.31. As the next step, we performed CRISPRi on rs28684409 and conducted RNA-seq to identify differential gene expression associated with this variant.