a, An illustrative LocusZoom plot of eQTLs for DACT3 gene expression in dorsolateral prefrontal cortex. Both the DACT3 gene promoter region and the AP2S1 gene promoter that contains significant eQTLs are highlighted in translucent orange, dots along the LocusZoom plot represent SNPs, and their significance of association with the DACT3 gene expression is plotted along the left y-axis. Dots are also color-coded based on their LD score with a tag SNP (rs78730097). The blue line indicates the estimated recombination rate, as plotted along the right y-axis. Gene expression levels detected by RNA-seq and RefSeq genes are plotted below the LocusZoom plot. b, Barplots showing the eQTL associations between the SNP rs78730097 and surrounding genes, showing the most significant association with the distal gene DACT3. Y-axis indicates –log10(eQTL association p value) obtained from GTEx database. c, d, Barplots showing FPKM values of distal target gene expressions upon deletion of core promoter regions of the ARIH2OS (f) and the ZNF891 (g). Two biological replicates of one mutant clone for the NCKIPSD (n=2) and two biological replicates of three mutant clones for the ZNF84 (n=6) were measured using RNA-seq, respectively. FDR-adjusted p value obtained from cuffdiff is shown together. N.S indicates statistically non-significant. e, Barplots showing FPKM values of two nearby genes of the ARIH2OS and one nearest gene of the NCKIPSD (y-axis) upon deletion of core promoter regions of the ARIH2OS. The ARIH2, a DNA fragment sharing gene with the ARIH2OS, is excluded. FDR-adjusted p value obtained from cuffdiff between WT and mutants for biological replicates (n=2) is shown together. Corresponding gene name is shown on the top of barplots. f, The relative mRNA expression levels of distal target genes (orange) and nearby genes (gray) of promoter-proximal eQTLs quantified by RT-qPCR are shown. Error bars indicate standard deviation from total six mutant clones for two separate sgRNAs with three mutant clones for each. Y-axis indicates mean values. One-sided KS-test p value is 6.14e-06 for the ABCF3 gene, 0.716 for the EIF4G1 gene, 6.14e-06 for the TOP3A gene, 0.862 for the LLG1 gene, 6.14e-06 for the SEC16A gene, 0.963 for the PMPCA gene, 0.552 for the SDCCAG3 gene, 1.00 for the ZFYVE21 gene (*** p value < 0.001).