(a, c, e). ExPecto expression effect prediction prioritizes putative causal SNPs in inflammatory bowel disease (a), Behcet’s disease(c), and chronic hepatitis B infection (e) GWAS loci. Linkage disequilibrium r2 scores between the reported variant and LD variants in the study population were shown in the top panel (variants are indicated by the × symbols) and the predicted expression effects (maximum across tissues) were shown in the bottom panel (variants are indicated by the dot symbols). The upper panels (GWAS-associated variants) showed the reported SNP(s) from the GWAS studies, indicated by the dashed lines, and all variants in LD with this variant (r2 > 0.25). The lower panels (ExPecto predicted effect) showed the predicted effects of all LD variants and the ExPecto-predicted causal variant is indicated by the dashed line.
(b, d, f) Luciferase reporter assay test verified predicted differential transcriptional regulatory activities of sequence elements with the risk allele and with the non-risk allele of prioritized variants, while showing no difference for the GWAS lead variants. Three top prioritized variants near IRGM– (b), CCR1(d), and HLA-DOA (f) showed differential transcriptional regulatory activity in the predicted direction while the reported GWAS SNPs show either no transcriptional activation activity or no detectable activity alteration. Luciferase activity is normalized by the empty vector, which is indicated by the dotted line. Statistical significance was based on two-sided t-test. Each allele was tested with at least 11 total replicates from 3 independent experiments (n=11 for the rs7616215 non-risk allele, n=12 for all other alleles). Central values of the boxplot represent the median, box extends from 25th to 75th percentiles, and whiskers extend to the maximum and minimum values.