We performed allele-specific correlation analyses across all probes with GSDMA expression, with probes deemed to be associated if P < 1 × 10−6, equivalent to Bonferroni-corrected P < 0.05. We observed 50 probes (corresponding to 40 genes; table S6) with expression significantly correlated with GSDMA in individuals homozygous for the CC genotype but with no association in the TT genotype (P > 0.01). The most significant probes mapped to SLCO2B1 (Fig. 6G), an organic ion transporter implicated in the transport of large molecules including eicosanoids, leukotrienes, steroids, and certain drugs (52). Pathway analysis of these genes showed the top-upstream regulators to be IL13 (P = 1.5 × 10−8), IL6 (P = 1.6 × 10−7), and CSF1 (P = 2.0 × 10−7), strongly implicated in asthma pathogenesis, inflammatory responses, and white cell count, respectively. These data suggest that certain risk alleles can alter the correlated gene expression profiles of specific genes in a context-specific manner, possibly removing such genes from their normal regulatory influences. More generally, this association illustrates how eQTL defined for innate immune stimuli can potentially further inform understanding of organ-specific disease.
