(a) Categorisation of 654 pQTL into four classes according to their putative mechanism: gene expression effect (i.e. replicated at eQTL level), transcript-isoform specific effect (i.e. not replicated at eQTL level, but significant at transcript isoform level), protein-altering variant (i.e. at least one inframe variant in LD with lead pQTL variant) without expression effect at RNA level, and without any putative mechanism identified. (b) Example pQTL without eQTL replication (rs6663; gene MMAB), with a directional opposite effect on a coding and non-coding isoform (cyan: ENST00000540016; grey: ENST00000537496), resulting in no overall change in gene expression level. (c) The pQTL variant (rs1051061) is a protein-altering variant associated with VRK2 protein abundance (below), and lacks detectable effect on RNA expression. The pQTL signal is observed across 15 peptides spanning the VRK2 protein sequence (above, left). This variant is associated with schizophrenia risk, and is located at the kinase active site, proximal to the proton acceptor residue (above, right). The dashed line and the grey box indicate the genomic positions of the lead QTL and of the gene. (d) Enrichment of RNA-independent pQTL in different categories of predicted variant effects, using gene variants in high LD with pQTLs (proxy gene variants; r2 >0.8; within the cis gene boundaries). Enrichment calculated using Fisher’s exact test.
Figure 3—source data 1. tQTL_results.Consists of variants mapped at RNA, transcript isoform resolution, for genes detected at both RNA and protein levels. The table columns are analogous to
Figure 2—source data 1 pQTL_results.
Figure 3—source data 2. pepQTL results.Consists of variants mapped at the protein level, peptide resolution, for genes detected at both RNA and protein levels. The table columns are analogous to
Figure 2—source data 1 pQTL_results.