Fig. 1: Identification of TET2 as a kidney disease risk gene.
a LocusZoom plots of eGFR GWAS (genotype and eGFRcrea association, n = 1,746,932) and fine mapping for chr4: 105,934,478-106,315,964. Each dot represents a SNP, with color indicating LD association. b LocusZoom plots of eGFR GWAS (genotype and eGFRcrea association, n = 2.2M), kidney CpG cg11878490 meQTL (genotype and cg11878490 methylation association, n = 443), and kidney TET2 eQTLs (genotype and TET2 expression association, n = 686)8. The y-axis displays the -log10 (p-values) of association tests from GWAS, meQTL, and eQTLs studies. c Genotype (rs6533181, x-axis) and normalized CpG methylation (cg11878490, y-axis) in human kidneys (n = 443). The effect size (Beta) is 0.51. Center line represents the median, the box limits show 25th and 75th percentiles, and whiskers extend to 5th and 95th percentiles. P-value was derived from linear regression meQTL model. d From top: Gene browser view of the eGFR GWAS SNPs in the specified regions; single-nucleus Assay for Transposase-Accessible Chromatin using sequencing (snATAC-seq) analysis of chromatin accessibility of human kidneys, including S1, S2, and S3 segments of the proximal tubules (PT-S1, PT-S2, PT-S3), loop of Henle (LOH), distal convoluted tubule (DCT), connecting tubule (CNT), intercalated cells (IC), collecting duct principal cell types (PC), podocytes (Podo), endothelial cells (Endo), immune cells (Immune), lymphocyte (Lymph). Human kidney histone modifications by chromatin immunoprecipitation (ChIP-seq) and chromatin states are also shown. e Relative transcript levels of TET2 after CRISPR-mediated deletion of the locus, with a sample size of n = 3. GAPDH was used for normalization. Data are shown as mean ± SEM and were analyzed using one-way ANOVA followed by Tukey’s post hoc test for multigroup comparison. The diagram was created with BioRender.com. Source data are provided as a Source Data file.
