International journal of women's health
Plasma Proteome-Wide Mendelian Randomization with Multi-Layer Triangulation Identifies Druggable Targets for Uterine Leiomyoma
Von Wang X, Yao G und Ding W.
Inhalt auf Englisch
Abstract
Background
Uterine leiomyoma (fibroids) is the most common benign tumor in women and the leading indication for hysterectomy, yet medical therapy remains limited and largely hormonal. Whether circulating proteins causally influence fibroid risk, and could therefore be repurposed as drug targets, has not been examined proteome-wide.
Methods
We performed cis-pQTL drug-target MR using plasma protein quantitative trait loci from the UK Biobank Pharma Proteomics Project (Olink; 2923 proteins; n=54,219). Uterine leiomyoma was the outcome in two GWAS: FinnGen R12 (42,107 cases/239,957 controls; discovery) and the European subset of Kim et al 2025 (53,711 cases/380,441 controls; second cohort, partly overlapping). Proteins passing Benjamini-Hochberg correction were prioritized by colocalization (PP4>0.8) in both cohorts across a grid of priors, then triangulated by summary-data-based MR, Steiger filtering, reverse MR, cross-platform SomaScan pQTL, phenome-wide scanning, fibroid-versus-myometrium expression, cross-ancestry look-up and druggability annotation.