Fig. 4

Phosphopeptide abundance can be regulated by substrate abundance dependent or non-substrate abundance dependent mechanisms. A Diagram showing how the genetic effect resulting in phQTL detection may be regulated by either parent protein abundance (batch corrected log₂ intensity) changes (Mechanism 1) or by phosphorylation stoichiometry (Mechanism 2) or both. B Genome scans for GAS2 and GAS2 pS283 in kidney tissue. C Path diagram of GAS2 pS283 abundance regulation in kidney tissue. D The PWK allele of the GAS2 pS283 phQTL drove low phosphopeptide abundance in kidney tissue. Data were categorized based on the founder haplotye at the identified pQTL. E Abundances of overall GAS2 and GAS2 pS283 were highly correlated (r = 0.99). Points are colored based on founder haplotype at Gas2. F Overall abundance of GAS2 and adjusted abundance (residual from regression of batch corrected log₂ intensity) of GAS2 pS283 were not correlated (r = 2.4e−17). Points are colored based on founder haplotype at Gas2. G Abundance of GAS2 pS283 and adjusted abundance of GAS2 pS283 were not correlated (r = 0.02). Points are colored based on founder haplotype at Gas2. H Genome scans for MCAT and MCAT pS41 in heart tissue. I NZO alleles at Pkd1 drove the low abundances of MCAT pS41 in heart tissue. Colors denote the founder haplotype of additive allele effects at the identified pQTL of MCAT pS41. J Mediation analysis identified PDK1 expression as the mediator of MCAT pS41 abundances. Each gray dot is a mediation score representing the MCAT pQTL LOD score conditioned on a protein as candidate mediator. K Path diagram of MCAT pS41 abundance regulation in heart tissue. L NZO alleles at Pkd1 drove the low abundances of PDK1 in heart tissue. Colors denote the founder haplotype of additive allele effects at the identified pQTL of MCAT pS41. M The adjusted abundances of MCAT pS41 and PDK1 were highly correlated (r = 0.86) in heart tissue. N Mediation analysis identified PDK1 as the mediator of several phQTL in heart, kidney, and liver tissue, respectively