Fig. 3

Functional characteristics of the African-specific novel variants on the high-risk asthma haplotype. A rs113282230, as a representative of the novel variants, is an eQTL for GSDMA but no other genes in upper airway epithelial cells (see Table 3 for results with all nine variants and Additional file 2 for results with all genes). BUpper panel: Chromosomal region from the 26.3-kb critical region (thick black bar) to the GSDMA gene on chromosome 17q12-q21. Vertical lines at the top show the locations of all variants in the critical region. The location of the four genes in the region, showing pcHi-C interactions (red arc) from a region in intron 1 of ORMDL3 to GSDMA. H3K27ac peaks (read counts; light blue tracks) in primary normal human epidermal keratinocytes (NHEK) (ENCODE) are shown in a region overlapping with the pcHi-C capture. Lower panel: Close-up of the 26.3-kb critical region. The nine African-specific variants enriched on haplotype 4 and eQTLs for GSDMA are shown in red. The same HEK27ac peaks as in upper panel, in addition to tracks of DNase clusters across all ENCODE cell lines, are shown. The darker the tracks the denser the DNase cluster. Two of the nine variants, rs113282230 and rs113571956, overlap with the marks of an active enhancer (H3K27ac), open chromatin (DNAse), and a putative enhancer (pcHi-C). See Fig. 4 and Additional file 1: Table S7 for additional annotations in airway epithelial cells and Additional file 1: Fig. S13 and Table S8 for additional annotations in immune cells