Potential Drug Targets and Causal Plasma Proteins Related to Preeclampsia Identified by Mendelian Randomization.

Background: Preeclampsia (PE) is a complication of pregnancy characterized by hypertension, with limited therapeutic options and variable treatment response. Identifying novel drug targets is urgently needed. Method: We performed Mendelian randomization (MR) to explore potential drug targets for PE using data from the UK Biobank (nCase = 184, nControl = 361,010) and the FinnGen database (nCase = 7,377, nControl = 211,957). Genetic instruments for pQTLs were obtained from five proteomic studies. Bayesian colocalization analysis and summary-data-based MR (SMR) analysis were performed to assess the causal relationship between two related signals (protein levels and PE risk). We further conducted single-cell type expression analysis and phenome-wide MR. In addition, a protein-protein interaction network of key genes was constructed Results: At a significance level of Conclusion: Our MR analysis suggested that the plasma proteins KRT18, FYN, RANBP1, AMIGO1, and ARG2 had causal effects on PE risk. These findings indicated that these five proteins might be promising druggable targets for PE and warrant further clinical therapy, especially KRT18.