Mapping pQTL Mapping Proteins Peptides MS/MS Compare ? Munger et al. 2014 Chick*, Munger* et al. Nature, 2016 How does genetic variation inﬂuence transcript and protein abundance in the liver and kidney? Compare kidney to liver
Mediation Analysis RNA Protein QTL trans cis RNA Protein Target Causal Intermediates RNA Protein trans QTL cis Target Target Protein ~ pQTLdistant Target Protein ~ pQTLdistant + MediatorProtein x 8000 proteins Target Protein ~ pQTLdistant + MediatorRNA x 21000 Transcripts X
but… – Most local variants that affect transcript levels do not affect protein levels. • Post-transcriptional mechanisms underlie all but a few of distant pQTL. – Very few distant pQTL shared by liver and kidney. • Mediation analysis can identify protein intermediates that confer significant or subtle effects on protein abundance. • Tissue-specific local e/pQTL drive tissue-specific distant pQTL.