Fine-mapping within eQTL Credible Intervals by E-CROPseq

Precise identification of causal variants within credible intervals of eQTL associations is needed to identify regulatory GWAS variants. We show that CROPseq, namely multiplex CRISPR-Cas9 genome editing combined with single cell RNAseq, is a viable strategy for fine mapping regulatory SNPs. Mutations were induced nearby 67 SNPs in three genes, two of which, rs2251039 and rs17523802, significantly altered CISD1 and PARK7 expression, respectively, and overlap with chromatin accessibility peaks. Single cell RNA-seq profiles of HL60/S4 infected by 67 gRNA CROP-seq lenti-viral libraries of two biological replicates. Each gRNA targets to candidate eSNPs for comprehensive eQTL screening.