Leveraging pQTL-based Mendelian randomization to identify new treatment prospects for primary biliary cholangitis and primary sclerosing cholangitis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38809509", "kind": "science-record", "revision": 2, "content_hash": "sha256:cba1dea9ca08bb6a95506277c7a0c131a438e0d5b58009a91b4eda2495c702bf", "created_at": "2026-11-01T19:20:46Z", "updated_at": "2026-11-01T21:33:11Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Leveraging pQTL-based Mendelian randomization to identify new treatment prospects for primary biliary cholangitis and primary sclerosing cholangitis.", "doi": "10.18632/aging.205867", "pmid": "38809509", "authors": ["Lei Dai", "Yunyan Ye", "Joseph Mugaany", "Zetong Hu", "Jing Huang", "Changjiang Lu"], "journal": "Aging", "year": 2024, "abstract": "Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are autoimmune disorders characterized by progressive and chronic damage to the bile ducts, presenting clinicians with significant challenges. The objective of this study is to identify potential druggable targets to offer new avenues for treatment. A Mendelian randomization analysis was performed to identify druggable targets for PBC and PSC. This involved obtaining Cis-protein quantitative trait loci (Cis-pQTL) data from the deCODE database to serve as exposure. Outcome data for PBC (557 cases and 281,127 controls) and PSC (1,715 cases and 330,903 controls) were obtained from the FINNGEN database. Colocalization analysis was conducted to determine whether these features share the same associated SNPs. Validation of the expression level of druggable targets was done using the GSE119600 dataset and immunohistochemistry for clinical samples. Lastly, the DRUGBANK database was used to predict potential drugs. The MR analysis identified eight druggable targets each for PBC and PSC. Subsequent summary-data-based MR and colocalization analyses showed that LEFTY2 had strong evidence as a therapeutic candidate for PBC, while HSPB1 had moderate evidence. For PSC, only FCGR3B showed strong evidence as a therapeutic candidate. Additionally, upregulated expression of these genes was validated in PBC and PSC groups by GEO dataset and clinical samples. This study identifies two novel druggable targets with strong evidence for therapeutic candidates for PBC (LEFTY2 and HSPB1) and one for PSC (FCGR3B). These targets offer new therapeutic opportunities to address the challenging nature of PBC and PSC treatment.", "claims": [{"id": "claim-method", "statement": "Two-sample Mendelian randomization analysis was conducted using the TwoSampleMR package [29].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38809509", "locator": "sections[7] \"Two-sample Mendelian randomization\" paragraph 2", "quote": "Two-sample Mendelian randomization analysis was conducted using the TwoSampleMR package [29]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s. All data and original files in our work are freely available under a ‘Creative Commons BY 4.0’ license. All methods were carried out in accordance with relevant guidelines and regulations.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38809509", "locator": "sections[14] \"Availability of data and materials\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s. All data and original files in our work are freely available under a ‘Creative Commons BY 4.0’ license. All methods were carried out in accordance with relevant guidelines and regulations."}], "state": "complete"}, {"id": "claim-target-result", "statement": "This study identifies two novel druggable targets with strong evidence for therapeutic candidates for PBC (LEFTY2 and HSPB1) and one for PSC (FCGR3B).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38809509", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "This study identifies two novel druggable targets with strong evidence for therapeutic candidates for PBC (LEFTY2 and HSPB1) and one for PSC (FCGR3B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "This study identifies two novel druggable targets with strong evidence for therapeutic candidates for PBC (LEFTY2 and HSPB1) and one for PSC (FCGR3B).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:38809509"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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All data and original files in our work are freely available under a ‘Creative Commons BY 4.0’ license. All methods were carried out in accordance with relevant guidelines and regulations.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s. All data and original files in our work are freely available under a ‘Creative Commons BY 4.0’ license. 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