Fig. 3: eQTL sharing between iPSC-PPC, adult islets, and adult whole pancreas.
a Bar plot showing the number of tissue-unique egQTLs identified in fetal-like iPSC-PPC, adult islets and adult whole pancreas. b Bar plot showing the number of egQTL modules for each annotation. c Top panels: Enrichment (odds ratio) of iPSC-PPC singleton and combinatorial egQTLs in hESC-derived PPC chromatin states14. Bottom panels: Enrichment (odds ratio) of iPSC-PPC singleton and combinatorial egQTLs in adult islet chromatin states54. Enrichment was calculated using a two-sided Fisher’s Exact Test comparing the proportion of candidate causal variants overlapping the chromatin states versus a background of randomly selected 20,000 variants at various PP thresholds. P-values were Benjamini-Hochberg-corrected and considered significant if the corrected p-values < 0.05 (indicated by asterisk, Supplementary Data 12). d CDC37L1-DT locus showing an iPSC-PPC-unique singleton egQTL overlapping an adult islet active promoter region. Lower panel shows the positions of active promoters in the adult islets. e, f The chr3:148903264-148983264 locus (gray rectangle) is an example of an “iPSC-PPC-unique” module (module ID: GE_3_1) associated with CP and HPS3 expression. g, h The chr15:57746360-57916360 locus (gray rectangle) is as an example of an “adult islet-unique” module (module ID: GE_15_13) associated with GCOM1, MYZAP, and POLR2M expression. GCOM1 was not expressed in adult whole pancreas and therefore, was not tested for egQTL association. i, j The chr5:146546063-146746063 locus (gray rectangle) is an “adult whole pancreas-unique” egQTL module (module ID: GE_5_32) associated with STK32A and STK32A-AS1 expression. STK32A-AS1 was not expressed in iPSC-PPC and therefore, was not tested for egQTL association. Panels e, g, i display the egQTL modules as networks in which the egQTL associations (nodes) are connected by edges due to colocalization (PP.H4 \(\ge\) 80%). For panels d, f, h, and j, the X-axis represents variant positions while the Y-axis shows the −log10(eQTL p-value) for the associations between the genotype of the tested variants and gene expression. For plotting purposes, we assigned 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.
