Association with PPM1H. (A) Top: close-up of the 12q14 signal. Middle: chromatin looping interactions in CD34⁺ cells with standard and internal promoter (red arches; y-axis indicates PCHi-C P-score). Bottom: positive correlation between PPM1H expression across sorted blood cell populations and ATAC-seq signal⁴⁵ (100 bp sliding window) in an ∼500-bp-long chromosomal segment in intron 1 (red peak)⁴⁵ (y-axis indicates false discovery rate for Pearson correlation). (B) Four credible set variants (supplemental Table 9) map to the identified segment, which is accessible in HSCs, MPPs, CMPs, and MEPs (y-axis indicates ATAC-seq signal). (C) Luciferase activities of the 4 candidate causal variants in K562 cells (3 biological replicates). P values for one-sided Student t test in the cis-eQTL direction. Data normalized to empty vector control (Ctrl). (D) MYB motif logo; rs772557[A>G] alters a critical recognition base. (E) Chromatin immunoprecipitation with massively parallel DNA sequencing for MYB in Jurkat cells (rs772557-heterozygous) showing exclusive pull-down of rs772557-G reads. (F) siRNA knockdown of MYB in K562 cells attenuates rs772557-G luciferase activity (3-4 biological replicates). P value is for one-sided Student t test. (G) CRISPR/Cas9 disruption of rs772557 (supplemental Figure 16) in K562 cells (5 biological targeting replicates; 7 biological control replicates). P values are for one-sided Student t test. (H) Coexpression of PPM1H and MYB across blood cell types. Data are bulked single-cell messenger RNA-seq data from 35 582 blood and bone marrow mononuclear cells.¹⁷ (I-J) CD34⁺ cell RNA-seq data revealed stronger correlation between MYB and PPM1H expression in rs772557-G homozygotes (n = 27) than in rs772557-A homozygotes (n = 37). Data are log₂-transformed fragments per kilobase of transcript per million mapped reads (FPKM) values, median-centered per genotype group. P and r values are for Pearson correlation. a.u., arbitrary units; B, B cells; Baso, basophil; CD4, CD4⁺ T cells; CD8, CD8⁺ T cells; CLP, common lymphoid progenitors; Cyc, cycling cells; DC, dendritic cells; ERY, erythroid progenitors; GMP, granulocyte-monocyte progenitors; LMPP, lymphoid-primed multipotent progenitors; mDC, myeloid dendritic cells; Mono, monocyte; n.s., not significant; PC, plasma cells; pDC, plasmacytoid dendritic cells; PreB, pre–B cells; Neut, neutrophil; NK, natural killer cells.