The resolution of context-specific eQTL can also enable the identification and interpretation of new disease associations from existing GWAS. For the autoimmune disease–associated gene CARD9, we identified a second independent stimulus-specific eQTL following IFN-γ in addition to a constitutively active eQTL (Fig. 6, A and B, and fig. S12). The latter is tagged by peak SNPs that define a GWAS locus for inflammatory bowel disease and ankylosing spondylitis (45, 46). We hypothesized that if differential expression of CARD9 is the functional mechanism underlying observed GWAS signals, the independent IFNγ-specific eQTL may additionally show evidence of disease association. A large cohort of Crohn’s disease (CD) patients and controls (46) confirmed that the constitutive CARD9 peak eQTL is associated with a risk allele for CD [rs4077515, PGWAS 2.2 × 10−20 odds ratio (OR) 1.25 (95% confidence interval, 1.20 to 1.30)]. Notably, conditional analysis demonstrated that the induced CARD9 peak eQTL was further associated with an independent signal of protection for CD [rs11145766 shows independent association with reduced risk of CD, P = 3.7 × 10−9 GWAS OR 0.73 (0.63 to 0.84)] (Fig.
