Relationships between co-expression modules, cytokines, and differentially expressed gene signatures.

<p><b>A</b>) Association between gene modules and cytokine production, with the color intensity indicating p-value (–log10, BH-adjusted) from linear regression between the modules’ eigengenes and the level of cytokine, and color indicating the correlation direction (red = positive, blue = negative). <b>B)</b> Enrichment of the co-expression modules in differentially expressed gene signatures, with the color intensity indicating p-value (–log10, BH-adjusted) from Fisher’s exact test for modules’ enrichments in the DEG signatures, and color indicating whether the genes in the signature were up-regulated (red) or down-regulated (blue). Module size (number of genes) is indicated in parenthesis after the label; the color scale (p-value) is truncated at ±10 (max is 163).</p

Immune Annotation analysis of the differentially expressed gene signatures.

<p>The color intensity indicates the Immune Annotation Score and the values are the odds ratios from Fisher’s exact tests with BH adjusted p-value < 0.1 for the given test. A. Level 1 (Cells), B. Level 2 (Cell Subsets), C. Level 3 (Activation Status), D. Level 4 (TLR-activated myeloid cells). The color indicates whether the genes in the signature were up-regulated (red) or down-regulated (blue). The results are shown for twelve of the total 24 DEG signatures used in the analysis, and immune Annotation categories with at least a single category with BH adjusted p-value ≤ 0.1. Colored text highlights significant associations with the matching DEG signature. Inf = Infinite, all observations were within the subgroup.</p

Cytokine secretion by group and stimulation condition.

<p>Cytokine secretion by group and stimulation condition.</p

Enrichment of differentially expressed gene signatures for transcription factor targets.

<p>Enrichment of the DEG signatures (top 200 by FC from top 500 by p-values) for transcriptional factor target gene sets, with Chip-X (ChIP-chip, ChIP-seq, ChIP-PET and DamID) derived ChEA set from human based experimental data in <b>A)</b>, ChEA set from rodent based experimental data in <b>B)</b>, and computationally predicted TRANSFACv.1 set in <b>C)</b>. The color intensity indicates–log10 of the FDR adjusted p-values and the indicated values are odds ratios (Fisher’s exact test). The color indicates whether the genes in the signature were up-regulated (red) or down-regulated (blue). The results are shown for only twelve (out of the total of 24 used in the analysis) DEG signatures, and only the TF target sets with at least a single enrichment with BH adjusted p-value ≤0.0001 for A) and B) and ≤0.05 for C), clustered according to the similarity of the enrichment pattern.</p

Immune Annotation enrichment in five egg allergy-associated co-expression modules.

<p>Enrichment results are shown for A) Level 1 immune cell types; B) Level 2 immune cell sub-types; C) Level 3 activation state of immune cell types; and D) Level 4 myeloid cell stimulation. The color intensity indicates the Immune Annotation Score and the values are the Fisher’s exact tests’ Odds Ratios for tests with BH adjusted p-value ≤ 0.10. Only categories with at least one significant result are included. Inf = Infinite, all observations were within the subgroup.</p

Differential expression of interferon response gene sets.

<p>Differential expression of eleven genes from the HALLMARK_ INTERFERON_ALPHA_RESPONSE (including 7 genes also in INTERFERON_GAMMA_RESPONSE, on the left) gene sets overlapping with the DEG signatures (top 200 by FC from top 500 by p-values). Color intensity and values indicate the nominal significance of the differential expression analysis, with values corresponding to negative logarithm of p-values (included for p-values < 0.05). The color indicates whether the genes in the signature were up-regulated (red) or down-regulated (blue).</p

Enrichment of differentially expressed gene signatures in Hallmark functional annotation categories.

<p>Enrichment of selected DEG signatures (top 200 by FC from top 500 by p-values) in Hallmark functional categories, with the color intensity indicating–log10 of the BH adjusted p-value and the values are odds ratios from Fisher’s exact tests. The left 3 signatures indicate EW vs. M for each clinical group, while the right 3 signatures indicate the difference in differential (EW vs. M) gene expression between groups. The color indicates whether the genes in the signature were up-regulated (red) or down-regulated (blue). Hallmark categories with at least a single enrichment with BH adjusted p-value ≤ 0.05 (out of total of 50) are shown, clustered according to the similarity of the enrichment pattern. Colored text highlights significant associations with the matching DEG signature.</p

Top 30 up regulated and down-regulated genes in BER_(EWvs.M) vs. AC_(Ewvs.M) differential expression sorted by fold change.

<p>Top 30 up regulated and down-regulated genes in BER_(EWvs.M) vs. AC_(Ewvs.M) differential expression sorted by fold change.</p

Additional file 2 of African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans

Additional file 2. Region-wide eQTL results in airway epithelial cells from 189 African American children in the URECA cohort

Additional file 1 of African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans

Additional file 1. Contains Supplementary Methods, Supplementary Tables (Table S1-10), and Supplementary Figures (Fig. S1-14), and corresponding references. Supplementary Methods. Descriptions of Populations. Building Consensus Sequences in the Critical Region. Table S1. Characteristics of the APIC and URECA Cohorts. Table S2. Predicted Haplotypes in CREW. Table S3. Haplotype Frequencies in Whole Genome Sequences. Table S4. Worldwide Frequencies of African-specific SNPs. Table S5. cis-eQTL Results for SNPs in or near GSDMA. Table S6. ENCODE Cell Lines and DNAse Clustering at pcHi-C Region. Table S7. pcHi-C Target Genes for African-specific Variants in Airway Epithelial Cells. Table S8. pcHi-C Target Genes for African-specific Variants in Airway Immune Cells. Table S9. Quantitative Trait Association Results in the APIC and URECA Cohorts. Table S10. African American Adult Asthmatics by Severity and Genotype. Figure S1. Overview of Study Design. Figure S2. ChromoPainter Analysis. Figure S3. ChromoPainter Visualization of Haplotype Breakpoints. Figure S4. ChromoPainter Display of the 17q12-q21 Region in Haplotype 4 Homozygotes. Figure S5. Ancestry PCA plots for APIC and URECA Children. Figure S6. eQTL Box Plots of rs28623237 Genotype and GSDMA Expression in CAAPA2. Figure S7. LD Plot of African-specific Variants and SNPs in or near GSDMA. Figure S8. eQTL Box Plots of rs113282230 Genotype and GSDMA Expression Conditioned on GSDMA SNPs. Figure S9. eQTL Violin Plots of rs235480 and rs1132828830 Genotypes on GSDMA and GSDMB Expression. Figure S10. LD Plot of the African-specific Variants and SNPs in the Core Region of The 17q12-q21 Locus. Figure S11. Chromatin Annotations in the Region Encoding the African-specific SNPs in ENCODE Cell Lines. Figure S12. eGenes for rs113282230 in Immune Cells. Figure S13. pcHi-C Data for rs113282230 in Immune Cells. Figure S14. Rs113282230 Genotype Effect on Asthma Prevalence by rs2305480 AA And GG Genotypes in APIC and URECA