al. [37] showed that SNPs in the region demonstrate domain-wide cis-regulatory effects suggesting long-range chromatin interactions and they found allele-specific differences in nucleosome distribution and binding of the insulator protein CTCF. A recent study also showed that asthma risk alleles on 17q21 were associated with increased ORMDL3 and GSDMA gene expression and elevated IL-17 secretion in cord blood mononuclear cells [38]. To refine the causal gene/variant, we have interrogated our eQTL results within this locus. Interestingly, the SNPs most strongly associated with the expression of ORMDL3 are located in the promoter (rs4794820) and intron 1 (rs12603332) of the ORMDL3 gene, but the P values are not convincing (most significant SNP rs4794820 P = 1.0×10−7). In addition the SNP rs4794820 is more strongly associated with mRNA expression levels of GSDMB (P = 9.3×10−12) and GSDMA (P = 2.2×10−46). Rs4794820 is located between ORMDL3 and GSDMA on 17q21 (see Figure 2a for the location of genes). Considering the transcription orientation of ORMDL3, GSDMA, and GSDMB, rs4794820 lies in the promoter of the three genes and is possibly a pleiotropic regulatory variant or, more likely, in LD with such a regulatory element. We observed a concordance between SNPs associated with transcript levels of
