# Unraveling the Causal Linkages of RBP7 and SCGB3A1 on Pelvic Organ Prolapse: Multifaceted Insights From Genome‐Wide Mendelian Randomization, Single‐Cell RNA Analysis, and Network Pharmacology

## TL;DR

This study explores how two genes, RBP7 and SCGB3A1, influence pelvic organ prolapse risk using genetic and cell-level data, and identifies potential drug targets.

## Contribution

The study integrates Mendelian randomization, single-cell RNA analysis, and network pharmacology to uncover causal gene links and drug candidates for pelvic organ prolapse.

## Key findings

- RBP7 high expression increases pelvic organ prolapse risk (OR 1.262, p = 0.002).
- SCGB3A1 high expression decreases pelvic organ prolapse risk (OR 0.907, p = 0.008).
- Fibroblast gene expression changes in collagen metabolism are significant for POP.

## Abstract

Pelvic organ prolapse (POP) is a common pelvic floor disorder in middle‐aged and elderly women. Its pathophysiology is complex, involving weakened pelvic floor muscles and connective tissues. There is a need to explore its underlying pathogenesis and develop effective treatments.

We integrated single‐cell sequencing (scRNA‐seq) data analysis with Mendelian randomization (MR) analysis. scRNA‐seq data of vaginal mucosal tissue were obtained from individuals with and without pelvic organ prolapse (POP); we then performed dimensionality reduction and cell subset identification. MR was conducted using GWAS summary statistics and eQTL data, following STROBE‐MR guidelines. We also performed protein‐protein interaction analysis, functional enrichment analysis, drug prediction, and molecular docking.

We identified RBP7 as a POP risk factor and SCGB3A1 as a protective factor. RBP7 high expression increased POP risk (IVW, OR 1.262, 95% CI 1.093–1.459, p = 0.002), whereas SCGB3A1 high expression decreased it (IVW, OR 0.907, 95% CI 0.844–0.975, p = 0.008). We found associated key genes and their biological processes and signaling pathways. We also predicted potential drugs and their binding affinities.

The study highlights the significance of fibroblast gene expression changes in collagen metabolism for POP. It identified risk and protective genes and explored potential drugs. Future research should verify SCGB3A1 functions in fibroblasts, conduct preclinical drug trials, and clarify POP molecular mechanisms.