ArticlePloS one2026
Exploration and discovery of treatment targets for primary biliary cholangitis based on plasma and cerebrospinal fluid proteomics: A multicenter mendelian randomization study.
Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrimary biliary cholangitis (PBC) is a chronic, progressive autoimmune cholestatic liver disease. Current first-line therapy, ursodeoxycholic acid (UDCA), yields suboptimal response rates, leaving many patients at risk of disease progression. Thus, novel therapeutic targets are urgently needed to slow PBC progression.
methodsWe performed two-sample Mendelian randomization (MR) to identify proteins causally associated with PBC risk, using protein quantitative trait loci (pQTL) as genetic instruments. The discovery stage utilized PBC genome-wide association study (GWAS) summary statistics from Cordell et al., followed by replication in independent GWAS datasets from the IEU Open GWAS project and the FinnGen consortium. pQTL data were drawn from large-scale plasma (N = 2,656) and cerebrospinal fluid (CSF; N = 184) proteomic studies. We also conducted sensitivity analyses, including Bayesian colocalization, reverse-causality testing, and phenotype scanning. Identified protein targets were further examined via protein-protein interaction (PPI) network analysis.
resultsThree proteins showed significant associations with PBC risk after Bonferroni correction (p < 6.35 × 10-5). Elevated plasma MANBA (odds ratio [OR] = 1.29, 95% confidence interval [CI] 1.20-1.40, p = 1.22 × 10-10) and CSF TNFSF15 (OR = 6.37, 95% CI 2.94-13.83, p = 2.79 × 10-6) were associated with higher PBC risk, whereas elevated plasma FCRL3 (OR = 0.79, 95% CI 0.73-0.86, p = 2.12 × 10-8) was associated with lower risk. Bayesian colocalization analysis indicated that these protein loci and PBC share the same underlying causal variants.
conclusionElevated plasma MANBA and CSF TNFSF15 levels were linked to increased PBC risk, while higher plasma FCRL3 was protective. Our findings nominate MANBA and TNFSF15 as potential therapeutic targets, while FCRL3 may serve as a protective biomarker for PBC management.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.