Identification of target genes for trait-associated SNPs overlapping with enhancers. a The transcription for reported and HiChIP genes in tubular cells. ** represents p value < 0.01. b The percentages of expressed genes in kidney tubules for reported and HiChIP genes based on protein levels from HPA. ** represent p value < 0.01. c The percentages of expressed genes for HiChIP genes in glomeruli or tubules based on protein levels from HPA. ** represents p value < 0.01. d Overlapping between HiChIP genes and reported genes. e Top: Virtual 4C of chromatin interaction around rs2049805. Bottom: epigenomic profile including ChromHMM, histone modifications in tubule cells, histone modification in kidney, chromatin interactions, and gene annotation track. Yellow bar highlights rs2049805 enhancer and anchor of virtual 4C. Blue bar highlights promoters interacted with rs2049805. f The effect size (β) of eQTL association between rs2049805 and THBS3, MUC1, MTX1, GBAP1, and GBA in tubulointerstitium. g Left: representative figures show edema of MTX1−/− zebrafish. Right: edema ratio of MTX1−/− zebrafish at different days. h qPCR of MTX1 transcription in zebrafish with RNP (sgRNA and CRISPR/Cas9 protein complex) of scramble, MTX1 sgRNA. Each group was repeated three times. i Electron microscope of kidney from zebrafish with scramble, MTX1 RNP. The red boxes (top) show increase space between tubules, and they are enlarged (bottom) to show the shed off of brush-border fragment. j Overexpression of human MTX1 mRNA partially rescue the edema. Each group was examined on two batches
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