Genome-wide association studies (GWAS) of phenotypes and plasma protein levels have successfully identified causal effectors of diseases. However, understanding how these proteins disrupt regulatory networks to influence disease risk remains a challenge. Post-translational modifications (PTMs) pervasively regulate protein functions. Many genes mapped to disease-risk loci and trans-protein quantitative trait loci (pQTLs) regulate PTMs, but their protein targets have not been comprehensively defined. To address this challenge, we developed an approach that involves GWAS of post-translationally modified sites on proteins to understand the cellular consequences of disease risk variants. In a proof-of-concept study, we performed a GWAS of protein levels and phosphorylation sites on proteins measured in human lung biopsies from 109 donors of European ancestry, utilising published mass spectra and whole genome sequences (Gillette et al. 2020, Satpathy et al. 2021). We identified 850 pQTLs and 656 phosphorylation site QTLs (phosQTLs) that passed genome-wide significance (P < 5x10-8). The nearest genes to the 579 genome-wide significant trans-phosQTLs were enriched in genes encoding receptors, ion channels, protein kinases and other signalling mediators such as GTPase activator proteins. For example, a 3’ untranslated region variant in IL18R1 was associated with phosphorylation of the kinase SIK2, which is known to regulate metabolism and inflammation, at serine 534 (P = 7x10-9). We observed pleiotropic phosQTL signals, indicating shared regulation of phosphorylation events, which included known and potential signalling relationships. We co-localised genetic signals between phosQTLs and phenotypes, leveraging large population GWAS to link signalling events with functional outcomes. Our study demonstrates the potential for genetic approaches to delineate cellular signalling networks and clarify how genetic variants rewire cells to increase disease risk. This method could be applied to map context-specific signalling events for diverse post-translational modifications in a range of cell types and tissues.