PRLR drug-target Mendelian randomization for endometriosis

Huihui Li
2026 · doi:10.5281/zenodo.21888581 · W7202204008
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A drug-target Mendelian randomization study of the prolactin receptor found that genetically predicted higher PRLR expression is significantly associated with increased endometriosis risk across multiple large-scale cohorts.

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This study employed drug-target Mendelian randomization to investigate the causal relationship between prolactin receptor (PRLR) expression and endometriosis risk. Using genetic instruments from eQTLGen, the researchers analyzed data across multiple large-scale cohorts including FinnGen, UK Biobank, and various meta-analyses, with findings validated through colocalization and SMR+HEIDI analyses. The results demonstrated that genetically predicted higher PRLR expression is significantly associated with an increased risk of developing endometriosis. This paper is centrally about endometriosis — specifically investigating the genetic causal role of the prolactin receptor in disease etiology.

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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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PRLR drug-target Mendelian randomization for endometriosis Authors/Creators Description This repository contains the complete analysis code, data, figures, and submission-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 instrument rs6451196), we performed drug-target MR for endometriosis across FinnGen releases (R8-R13), with replication in UK Biobank, the Sakaue 2021 cross-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 predicted higher 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 the associated manuscript upon publication. Files PRLR_EMs_zenodo_archive_2026-08-11.zip Files (11.1 MB) | Name | Size | Download all | |---|---|---| | md5:576fcde4ad57568b880a8b1cccb55ba1 | 11.1 MB | Preview Download |

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