Biosignatures of CH in DS. (A) Volcano plot displaying results of whole blood transcriptome analyses of individuals with T21 with (CH-DS) vs without CH. Differential expression, fold changes, and false discovery rate (FDR)–adjusted P values (padj) were calculated with DeSeq2. Horizontal dashed line indicates the statistical cutoff of adjusted P value < .1. (B) Heatmap displaying Z-score values for differentially expressed genes (DEGs) in individuals with T21 and with (CH) or without (Control) CH-DS. (C) Sina plots for select DEGs. (D) Heatmap showing results of gene set enrichment analysis (GSEA) of the transcriptome data. Orange denotes activation of the indicated pathways; violet indicates repression. (E) Volcano plot showing the results of plasma cytokine profiling using Meso Scale Discovery assays for 54 immune factors in individuals with DS with vs without CH. Fold-change and FDR-adjusted P values were calculated with a linear model. Horizontal dashed line indicates the statistical cutoff of adjusted P < .1. (F) Sina plots showning levels of select cytokines differentially abundant in the plasma of individuals with T21 and CH-DS. Boxes in panels C and F represent interquartile ranges and whiskers extend to 1.5× the interquartile ranges. Dn, down; NES, normalized enrichment score; UV, ultraviolet light.