Fig. 1: Gene and isoform eQTLs.

a Barplot showing the number of eQTLs for eGenes (left) and eIsoforms (right). Colors represent the number of eGenes with primary and conditional eQTLs (up to five conditional signals). b Barplot showing the distribution of PPA for each of the five colocalization hypotheses. All the colocalizations associated with hypothesis 0, 1, and 2 were likely underpowered, thus they were labeled as “not resolved (NR)”. The 1421 eIsoforms whose associated gene did not have an eQTL were labeled as “no eGene”. c, d Examples of (c) eQTL signal for an eGene (B4GALT7) that colocalizes with PPA = 1 with the eQTL signal of one associated eIsoform and (d) eQTL signal for an eGene (RNH1) that does not colocalize with the eQTL signal of one associated eIsoform. In each plot, X axis represents the −log₁₀ (eQTL p-value) for the associations between the genotype of each tested variant and gene expression, whereas the Y axis shows the −log₁₀ (eQTL p-value) for the associations between the genotype of each tested variant and isoform use. e Enrichment of eGenes compared with eIsoforms for overlapping intergenic regions, introns, promoters, UTRs, splice donor sites, splice acceptor sites (short = the first 5 nucleotides upstream of the splice site; long = the first 100 bp) and exons. P-values were calculated using Fisher’s exact test. Points (blue = enriched for eGenes; red = enriched for eIsoforms; gray = not significant) represent log₂ enrichment and horizontal lines represent 95% confidence intervals calculated using the fisher.test function in R. f, g Median normalized read depth signal of ADAM15 gene expression levels in iPSC-CVPCs. Different colors represent the genotypes of the lead eVariant for isoform ENST00000271836.10_1 (rs11589479, G > A). The blue rectangle in (f) is enlarged in (g). rs11589479 overlaps the splice donor site for exon 19 and its position is shown as a vertical dashed line in (g). The plots show that the exon whose splice site is affected by rs11589479 becomes expressed at lower levels when the variant is heterozygous or homozygous alternative, as it disrupts the splice site.