Fig. 4: Peptide level analysis of the rs2052534 SPINK5 pQTL.

a–c, Violin plots of a splice QTL from GTEx (a), SPINK5 at the protein level (b) and SPINK5 at the peptide level for representative peptides of the four protein groups (c). d, Forest plot of the peptide level meta-analysis. e, UniProt isoforms and protein groups. f, Gene structure indicating the alternative splice forms (black, green, red and blue) from Ensembl with the position of rs2052534 indicated. The C-allele of rs2052534 leads to a higher exon excision ratio and results in lower levels of the peptide QVQNEAEDAK, which is specific for the intron-retaining Q9NQ38-3 isoform (note the reverse order of the alleles in a versus b and c). This SPINK5 pQTL illustrates how peptide level information can be used to identify different isoform QTLs. However, it also reveals current limitations in the automated quantification of such isoforms, because this information did not translate to the protein level QTL, which in this case reflects the average of the isoform signals. A multiple alignment of all detected peptides is shown in Supplementary Table 11, violin plots for all peptide associations are provided as Supplementary Data 5 and regional association plots are in Supplementary Figure 16.