Figure 6.
PU.1 motif-altering deletion rs5827412 at the LRRC25 locus associated with lower monocyte counts
(A) Association Z scores of variants in the locus with PU.1 binding and monocyte percentage. The sign of the Z score is the effect direction of the AA of each variant. The points are colored by LD r2 with respect to rs5827412 (purple diamond).
(B) The effect of rs5827412 on the PU.1 motif. Dashes indicate gaps in the alignment, reflecting the short deletion.
(C) Negative allelic skew (i.e., reduced reporter activity) by rs5827412 in log2 fold change. Error bars indicate 95% confidence intervals. ∗: adjusted p < 0.05.
(D) A boxplot showing PU.1-dependent reduction in chromatin accessibility levels (CPM) at the regulatory element surrounding rs5827412 in control pro-B cell lines (SPI1+/+) and counterparts with SPI1 knocked out (SPI1−/−). Regions highlighted in yellow marks the accessible region corresponding to the boxplot. All data points are superimposed over the boxplot. n = 3 for each condition. ∗: DESeq2-adjusted p < 0.05.
(E) A boxplot showing LRRC25 expression levels (CPM) through monocyte differentiation. All data points are superimposed over the boxplot. CMP, common myeloid progenitor; GMP, granulocyte-macrophage progenitor.
(F) Mono LRRC25 eQTL association. Downward and upward triangles indicate the direction of effect (down- and upregulation, respectively) for variants with p < 1 × 10−3. A purple triangle and dashed line mark rs5827412.
(G) LRRC25 locus ATAC-seq tracks as fold enrichment over average (range, 0–40) for various blood cell types through monocyte differentiation. A purple diamond and dashed line mark rs5827412.