Integrated Genomic and GEO Data Analysis Reveals Therapeutic Targets for Rosacea.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40635520", "kind": "science-record", "revision": 3, "content_hash": "sha256:ce5a3af64b5738ad28f1f1b83cf1027cdcd2b563eb76e4a9debbe3cc8ebb7256", "created_at": "2026-11-01T20:30:44Z", "updated_at": "2026-11-01T22:14:20Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrated Genomic and GEO Data Analysis Reveals Therapeutic Targets for Rosacea.", "doi": "10.1111/jocd.70334", "pmid": "40635520", "authors": ["Xinrui Deng", "Sui He", "Huiyu Long", "Jinyuan Xiao", "Zhengchun Xie"], "journal": "Journal of cosmetic dermatology", "year": 2025, "abstract": "BACKGROUND: Rosacea is a chronic inflammatory facial disorder with limited therapeutic options, severely impacting patients' quality of life. The identification of druggable genes plays a crucial role in facilitating the development of effective therapeutic strategies.\nMETHODS: We conducted Mendelian randomization (MR) and Summary-based Mendelian randomization (SMR) analyses by integrating data on 5883 druggable genes, cis-expressed quantitative trait loci (eQTL) from blood and skin tissue (lower leg and suprapubic), and genome-wide association study (GWAS) data on rosacea to elucidate the causal relationship between druggable genes and rosacea. Robustness was confirmed via heterogeneity/horizontal pleiotropy tests, Steiger filtering, Bayesian colocalization analysis, and the heterogeneity in dependent instruments (HEIDI) analysis. The expression levels of identified druggable genes were validated using the GSE65914 data sets. Further analyses included protein-protein interactions (PPIs), functional enrichment analysis, phenome-wide association study (PheWAS), drug prediction, and molecular docking.\nRESULTS: MR and SMR analyses identified IRF1 and SLC22A5 as druggable genes for rosacea, with Bayesian colocalization strongly supporting shared causal variants. GEO data sets confirmed significant upregulation of IRF1 and downregulation of SLC22A5 in rosacea patients. PPIs and functional enrichment analyses revealed that IRF1 promotes inflammation by regulating immune cell activation and interferon signaling pathways; SLC22A5 regulates membrane transport and metabolic processes, and its dysregulation may lead to lipid homeostasis imbalance. PheWAS analysis indicated no other phenotypes associated with IRF1 and SLC22A5. Drug prediction and molecular docking verified the pharmacological value of IRF1 and SLC22A5.\nCONCLUSION: This study identified IRF1 and SLC22A5 as potential drug targets for the treatment of rosacea, and their significant therapeutic potential provides a critical foundation for the development of targeted therapies.", "claims": [{"id": "claim-method", "statement": "We performed a phenome‐wide MR study via the AstraZeneca PheWAS portal to investigate the potential side effects of IRF1 and SLC22A5.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40635520", "locator": "sections[19] \"Phenome‐Wide Association Analysis\" paragraph 2", "quote": "We performed a phenome‐wide MR study via the AstraZeneca PheWAS portal to investigate the potential side effects of IRF1 and SLC22A5."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The eQTL and GWAS data sets generated and/or analyzed during the current study are publicly available.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40635520", "locator": "sections[31] \"Data Availability Statement\" paragraph 2", "quote": "The eQTL and GWAS data sets generated and/or analyzed during the current study are publicly available."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The phenome-wide Mendelian randomization analysis found no significant associations between IRF1 or SLC22A5 and other phenotypes at genome-wide significance.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40635520", "locator": "sections[19] \"Phenome‐Wide Association Analysis\" paragraph 2", "quote": "The results showed that there was no evidence of a significant relationship between these two drug targets and other phenotypes in the PheWAS Portal at a genome‐wide significance level (p < 5E‐08)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The phenome-wide Mendelian randomization analysis found no significant associations between IRF1 or SLC22A5 and other phenotypes at genome-wide significance.", "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:40635520"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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