Fig 1.
Study design for the identification of plasma and CSF proteins causally associated with PBC.
Table 1.
MR results for plasma and CSF proteins markedly linked to PBC after Bonferroni-adjusted.
Fig 2.
A volcano plot was generated to identify 3 proteins as potential targets in PBC from a pool of 734 plasma proteins (A) and 151 CSF proteins.
(B) using the Wald ratio or inverse variance weighted method. CSF: cerebrospinal fluid, PVE: proportion of variance explained.
Fig 3.
External validation was conducted to assess the genetically supported associations between 3 potential proteins and PBC.
Odds ratios (ORs) were calculated to determine the increased risk of PBC per standard deviation (SD) increase in plasma protein levels and per 10-fold increase in CSF protein levels.
Table 2.
Sensitivity analysis on 3 potential causal proteins.
Fig 4.
Comparison analysis of MR estimates between plasma proteome and CSF proteome.
(A) Correlation analysis was performed on all 92 overlapping proteins in plasma and CSF. The horizontal and vertical gray lines represent 95% confidence intervals for MR estimates. The Spearman correlation coefficient was −0.099 (95% CI: −0.406, 0.278); (B) Spearman’s correlation coefficient was calculated using different cutoffs for P values to include MR estimates. The numbers on the left side of the black point indicated the number of proteins that overlapped.