Fig. 7: Pancreatic GWAS associations with fetal-specific alternative splicing.
a T1D-risk locus colocalized with a fetal-like iPSC-PPC-unique singleton eASQTL for MEG3 with the predicted causal variant rs56994090 (chr14:101306447:T > C, PP = 100%). b GWAS locus associated with HbA1c colocalized with an iPSC-PPC-unique singleton eASQTL for CDH3 with the predicted causal variant rs72785165 (chr16:68755635:T > A, PP = 6.8%). c GWAS locus associated with T2D-risk and BMI colocalized with an iPSC-PPC-unique eASQTL module (AS_13_2) for differential usage of three HMGB1 isoforms with a predicted causal variant rs3742305 (chr13:31036642:C > G, PP = 49.3%). In each panel, the X-axis represents variant positions while the Y-axis either shows the −log10(eQTL p-value) for the associations between the genotype of the tested variants and gene expression or the −log10(GWAS p-value) for the associations between the tested variants and the GWAS trait. For GWAS significance, we used −log10(5 × 10−8). For eQTL significance, we used a single p-value for gene-level significance after Bonferroni-correction (0.05/the number of independent variants tested in fetal-like iPSC-PPC; horizontal line). Red vertical lines indicate the positions of the lead candidate causal variants underlying the colocalization based on maximum PP. For loci that colocalized with multiple GWAS traits, we used the credible set that yielded the smallest number of variants to plot the “PP” fine-mapping panel.
