Exploring the Relationship Between 91 Inflammatory Cytokines and IgA Nephropathy Using a Two-Sample Mendelian Randomization Study and the Gene Expression Omnibus Database.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40322064", "kind": "science-record", "revision": 2, "content_hash": "sha256:7062dfad698749413135396a70c88dfe6a0c4da4d90e83211c80f16ddf9bdbfb", "created_at": "2026-11-01T20:30:29Z", "updated_at": "2026-11-01T21:35:08Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exploring the Relationship Between 91 Inflammatory Cytokines and IgA Nephropathy Using a Two-Sample Mendelian Randomization Study and the Gene Expression Omnibus Database.", "doi": "10.1155/mi/5142090", "pmid": "40322064", "authors": ["Manyi Wu", "Xingxin Yang", "Mengxiao Zou", "Xiaojing Cai", "Chunyu Pan", "Junhua Li", "Shuwang Ge"], "journal": "Mediators of inflammation", "year": 2025, "abstract": "Objectives: Previous research has demonstrated associations between various inflammatory cytokines and IgA nephropathy (IgAN). However, the causal relationships between them remain unclear. The purpose of this study is to extensively analyze the causal links between 91 circulating cytokines and IgAN. Methods: This study commenced with a two-sample bidirectional Mendelian randomization analysis. Genetic variations associated with 91 circulating inflammatory cytokines were extracted from genome-wide association study (GWAS) data involving individuals of European ancestry (n = 14824). In the corresponding GWAS dataset, the genetic variations for IgAN were obtained from a Finnish cohort of European ancestry, consisting of a case group (n = 653) and a control group (n = 411528). The findings from the Mendelian randomization analysis were subsequently subjected to preliminary validation using the GSE116626 dataset from the GEO database. Results: Our MR analysis indicates that transforming growth factor-alpha (TGF-alpha), leukemia inhibitory factor (LIF), and C-C motif chemokine 19 (CCL19) are linked to an increased risk of IgAN. There were no causal connections found when IgAN was used as an exposure and the 91 circulating inflammatory cytokines as outcomes. In addition, the GSE116626 dataset from the GEO database revealed significant upregulation of CCL19 in renal tissues from patients diagnosed with IgAN. Conclusions: This study shows a causal link between inflammatory cytokines and IgAN, suggesting that TGF-alpha, LIF, and CCL19 may act as upstream mediators in the pathogenic pathways of IgAN. The critical role of CCL19 in the pathogenesis of IgAN was further validated using data from the GEO database. However, whether these cytokines can be used to predict or ameliorate the progression of IgAN requires further investigation.", "claims": [{"id": "claim-method", "statement": "This study commenced with a two-sample bidirectional Mendelian randomization analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40322064", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "This study commenced with a two-sample bidirectional Mendelian randomization analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data Availability Statement\nThe data supporting this research are sourced from the FINNGEN database and the GEO database. The authors sincerely thank the relevant researchers for sharing the GWAS summary statistics included in this study. All the aforementioned data are publicly available.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40322064", "locator": "sections[18] \"Data Availability Statement\" paragraphs 1-2", "quote": "Data Availability Statement\nThe data supporting this research are sourced from the FINNGEN database and the GEO database. The authors sincerely thank the relevant researchers for sharing the GWAS summary statistics included in this study. All the aforementioned data are publicly available."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Genetically predicted TGF-alpha, LIF, and CCL19 levels were associated with increased IgAN risk (ORs 2.34, 2.47, and 1.66, respectively).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "When considering the 91 circulating inflammatory cytokines as exposures and IgAN as the outcome, the analysis results are shown in Figure 1. Seven genetically predicted inflammatory cytokines were associated with IgAN, with transforming growth factor-alpha levels (TGF-alpha, OR: 2.34, 95% CI: 1.39–3.93, p=0.0013), leukemia inhibitory factor (LIF) levels (OR: 2.47, 95% CI: 1.35–4.53, p=0.0035), C–C motif chemokine 19 (CCL19) levels (OR: 1.66, 95% CI: 1.12–2.45, p=0.012), and programmed cell death 1 ligand 1 levels (OR: 1.75, 95% CI: 1.09–2.80, p=0.019) serving as promoters, while C–C motif chemokine 20 levels (OR: 0.58, 95% CI: 0.37–0.91, p=0.014), monocyte chemoattractant protein-3 levels (OR: 0.67, 95% CI: 0.47–0.94, p=0.021), and Interleukin-13 levels (OR: 0.61, 95% CI: 0.39–0.97, p=0.035) acted as inhibitors."}, "evidence": [{"asset": "source:pmid:40322064", "locator": "sections[12] \"3.2. Investigating the Relationship Between 91 Circulating Inflammatory Cytokines and the IgA Nephropathy\" paragraph 2", "quote": "When considering the 91 circulating inflammatory cytokines as exposures and IgAN as the outcome, the analysis results are shown in Figure 1. Seven genetically predicted inflammatory cytokines were associated with IgAN, with transforming growth factor-alpha levels (TGF-alpha, OR: 2.34, 95% CI: 1.39–3.93, p=0.0013), leukemia inhibitory factor (LIF) levels (OR: 2.47, 95% CI: 1.35–4.53, p=0.0035), C–C motif chemokine 19 (CCL19) levels (OR: 1.66, 95% CI: 1.12–2.45, p=0.012), and programmed cell death 1 ligand 1 levels (OR: 1.75, 95% CI: 1.09–2.80, p=0.019) serving as promoters, while C–C motif chemokine 20 levels (OR: 0.58, 95% CI: 0.37–0.91, p=0.014), monocyte chemoattractant protein-3 levels (OR: 0.67, 95% CI: 0.47–0.94, p=0.021), and Interleukin-13 levels (OR: 0.61, 95% CI: 0.39–0.97, p=0.035) acted as inhibitors."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Genetically predicted TGF-alpha, LIF, and CCL19 levels were associated with increased IgAN risk (ORs 2.34, 2.47, and 1.66, respectively).", "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:40322064"], "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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