PRLR drug-target Mendelian randomization for endometriosis

Huihui Li
2026 · doi:10.5281/zenodo.21888582 · W7202199853
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This drug-target Mendelian randomization study found that genetically predicted higher prolactin receptor expression increases endometriosis risk, a finding supported by colocalization and replication across multiple cohorts.

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This study employs cis-expression quantitative trait locus Mendelian randomization to investigate the causal relationship between prolactin receptor expression and endometriosis risk. The researchers utilized summary statistics from large-scale genome-wide association studies, including data from eQTLGen, FinnGen, and the Rahmioglu 2023 endometriosis GWAS, alongside colocalization analyses to confirm shared genetic signals. The findings provide genetic evidence supporting the repurposing of prolactin receptor inhibition as a potential therapeutic strategy for treating endometriosis. This paper is centrally about endometriosis — specifically evaluating the genetic causality of the prolactin receptor pathway in disease pathogenesis.

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Abstract

This repository contains the complete analysis code, data, figures, andsubmission-ready manuscript for a drug-target Mendelian randomization (MR)study of the prolactin receptor (PRLR) and endometriosis risk. Study summary:Using cis-eQTL instruments for PRLR from eQTLGen (primary instrumentrs6451196), we performed drug-target MR for endometriosis across FinnGenreleases (R8-R13), with replication in UK Biobank, the Sakaue 2021cross-population meta-analysis, the Rahmioglu 2023 European meta-analysis(GCST90205183), and BioBank Japan. Findings were validated by colocalisation(PP.H4=90.6%), SMR+HEIDI, and GTEx tissue eQTL analyses. Genetically predictedhigher PRLR expression was associated with increased endometriosis risk(FinnGen R13: beta=0.227, 95% CI 0.136-0.317, P=7.1e-7; OR=1.26). Contents:- scripts/: analysis scripts (Python/R) for MR, colocalisation, SMR+HEIDI, sensitivity, and figure generation- results/: analysis outputs and summary tables- manuscript/: submission-ready manuscript- manuscript_ebiomedicine_reformatted_fixed.md/.docx: final main text- supplementary_reformatted_fixed.md/.docx: supplementary materials- figures_final/: main figures (Figure 1-5) in editable PDF and 300-dpi PNG- supplementary_figS1-S3: supplementary figures All analyses used publicly available summary-level data. Please cite theassociated manuscript upon publication.
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This repository contains the analysis code and figures for: "Repurposing Prolactin Receptor Inhibition for Endometriosis: Genetic Evidence from cis-eQTL Mendelian Randomization and Colocalisation" scripts/ — Analysis scripts (MR, colocalisation, Steiger test, cross-population validation)figures/ — All 6 main figures (PDF and PNG)manuscript/ — Manuscript formatted for eBioMedicine submission All summary statistics used are publicly available: - eQTLGen: IEU OpenGWAS (https://gwas.mrcieu.ac.uk) - FinnGen R9/R10/R13: Google Cloud Storage - Rahmioglu 2023 EMs GWAS: GWAS Catalog GCST90044085 - GTEx V8: GTEx Portal Huihui Li — [email protected]

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