Fig. 4

Genetic basis of miRNA expression upon immune activation. a Percentage of genes and miRNAs under genetic control, across various functional classes. For each gene class, 1000 bootstrap resamples were performed and the resulting distribution is shown as a boxplot. b Sharing of miR-QTLs and eQTLs across conditions. For the 122 miR-QTLs and 3802 eQTLs, number of conditions where a QTL is detected. c Example of an African-specific response miR-QTL. The rs75335466-T allele is associated with reduced expression of miR-146a-5p specifically upon stimulation by LPS and R848 (* t test p-value < 0.001). For clarity, data is shown only for African-ancestry individuals. d Localization of miR-QTLs. Left: Frequency of miR-QTLs that either overlap the mature miRNA (miRNA-altering, pink) or its hairpin (hairpin-altering, orange), or are located < 20 kb away from the miRNA hairpin (hairpin-flanking, yellow) or TSS (TSS-flanking, green). Remaining miR-QTLs are annotated as Distant (blue). Right: Distance of mir-QTLs from the mature miRNAs (x-axis) and its associated TSS (y-axis). Each miR-QTL is shown as a separate dot, colored according to its localization. Negative distance indicates that the miR-QTL is located upstream of the miRNA and/or TSS. Close-up view is shown for miR-QTLs located < 50 kb from the miRNA or TSS. (E–G) Impact of rs2910164 variant on miR-146a-3p isomiRs. e Genomic context and frequency of the rs2910164 variant. The rs2910164 C/G variant is shown with its neighboring hairpin sequence. Sequence of the canonical miRNA is displayed in black. The 2 most frequent isomiRs of miR-146a-3p are displayed below and denoted as (− 2; − 2), and (0; − 1) based on the coordinates of their start/end site relative to the canonical miRNA sequence. Note that the C/G substitution is not considered for the quantification of (− 2; − 2) and (0; − 1) isomiRs. Frequency of C/G alleles in our sample is shown in African- and European- ancestry individuals separately. f isomiR-QTL of miR-146a-3p. Ratios of (− 2;-2) and (0; − 1) isomiRs are shown for each genotype, in the R848 condition where the isomiR-QTL is the strongest. For clarity, other isomiRs are not displayed. g Overlap of miRNA targets predicted by miRNA for each possible isomiR