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. 2022 Dec 8;13:7592. doi: 10.1038/s41467-022-35354-7

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — All p-values are derived from two-sided t-tests and are not adjusted for multiple comparisons. A Genome-wide association -log10(p-values) for 9q22.1 variants associated with peripheral monocyte counts. The purple diamond represents the trait-associated deletion (9:88923551-88924152); large circles represent other SVs; and small circles represent single nucleotide variants (SNVs) or indels. Color indicates the linkage disequilibrium (LD) calculated in the analysis sample set between the trait-associated deletion and individual SVs and SNVs. B Distribution of accessible chromatin (by DNase I sequencing) and histone modifications (H3K27ac, H3K4me1 and H3K4me3) in primary CD14 + monocytes across indicated genomic regions from ENCODE²⁶. C Virtual 4C plot of long-range chromatin interactions anchored at the trait-associated, 9q22.1 deletion (9:88923551-88924152, upper panel) and the S1PR3 promoter region (9:91605763-91606263, lower panel), shown as a grey bar, in macrophages. Yellow line highlights the S1PR3 promoter region (upper panel) trait-associated, 9q22.1 deletion (lower panel). The observed and expected chromatin contact frequencies (or counts) are represented by the black and red lines, respectively. The left Y axis displays the range of chromatin contact frequency. The statistical significance (–log10(P-value)) of each long-range chromatin interaction is represented by the blue line, with its range listed in the right Y axis. The cell line or tissue specific FDR threshold (5%) is shown as a purple horizontal dashed line, and the more stringent Bonferroni threshold (P = 0.05) is shown as a maroon horizontal dashed line. D Long-range chromatin interaction between the trait-associated, 9q22.1 deletion and S1PR3 promoter calculated in 12 different cell types. MSC (mesendoderm), NPC (neural progenitor cell), HC (hippocampus), H1 (human embryonic stem cells), LV (left ventricle), PA (pancreas), SX (spleen), DLPFC (dorsolateral prefrontal cortex), LG (lung)³¹, GM (lymphoblast)⁷⁶, Mac (macrophages), Mon (monocytes)²⁷. The circle size represents the magnitude of the -log10 p-value while the color indicates S1PR3 mRNA level. TPM: transcripts per million.