Constructing a protein-protein interaction network for autoimmune liver diseases by integrating pQTL, rQTL, and mediation analyses - PubMed
7 hours ago
- #Mendelian randomization
- #Protein-protein interaction
- #Autoimmune liver diseases
- Study focuses on constructing a protein-protein interaction network for autoimmune liver diseases (AILDs) including PBC, PSC, and AIH.
- Utilizes protein quantitative trait loci (pQTLs), ratio QTLs (rQTLs), and mediation Mendelian randomization (MR) to map causal proteomic networks.
- Analyzed 2821 plasma protein-protein ratios (PPRs) and 2923 individual proteins from the UK Biobank Pharma Proteomics Project.
- Identified CD74 as having dual roles in AILDs, with elevated levels increasing PSC risk but certain CD74-PPRs offering protection.
- Mediation MR identified TRY3, GREM1, and TEK as mediators in the effects of CD74-related PPRs on AILDs.
- Protein-protein interaction networks highlighted interactions among CD74, amyloid precursor protein (APP), and endoglin (ENG).
- CD74/JAM2 PPR showed cross-disease relevance by lowering PSC-associated ulcerative colitis risk.
- Findings suggest CD74's direct elevation may promote disease, while its protein interactions mitigate risk, offering new therapeutic targets.