Integrated mendelian randomization analyses highlight AFF3 as a novel eQTL-mediated susceptibility gene in renal cancer and its potential mechanisms.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38886730", "kind": "science-record", "revision": 2, "content_hash": "sha256:226476b6cc4302dd3630a12744a1fdc0099733332c5e504756c9b1da4f66ad72", "created_at": "2026-11-01T20:28:57Z", "updated_at": "2026-11-01T21:33:18Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrated mendelian randomization analyses highlight AFF3 as a novel eQTL-mediated susceptibility gene in renal cancer and its potential mechanisms.", "doi": "10.1186/s12885-024-12513-1", "pmid": "38886730", "authors": ["Qiming Wang", "Shaopeng Chen", "Gang Wang", "Tielong Zhang", "Yulong Gao"], "journal": "BMC cancer", "year": 2024, "abstract": "BACKGROUNDS: A growing number of expression quantitative trait loci (eQTLs) have been found to be linked with tumorigenesis. In this article, we employed integrated Mendelian randomization (MR) analyses to identify novel susceptibility genes in renal cancer (RC) and reveal their potential mechanisms.\nMETHODS: Two-sample MR analyses were performed to infer causal relationships between eQTLs, metabolites, and RC risks through the \"TwoSampleMR\" R package. Sensitivity analyses, such as heterogeneity, pleiotropy, and leave-one-out analysis, were used to assess the stability of our outcomes. Summary-data-based MR (SMR) analyses were used to verify the causal relationships among cis-eQTLs and RC risks via the SMR 1.3.1 software.\nRESULTS: Our results provided the first evidence for AFF3 eQTL elevating RC risks, suggesting its oncogenic roles (IVW method; odds ratio (OR) = 1.0005; 95% confidence interval (CI) = 1.0001-1.0010; P = 0.0285; heterogeneity = 0.9588; pleiotropy = 0.8397). Further SMR analysis validated the causal relationships among AFF3 cis-eQTLs and RC risks (P < 0.05). Moreover, the TCGA-KIRC, the ICGC-RC, and the GSE159115 datasets verified that the AFF3 gene was more highly expressed in RC tumors than normal control via scRNA-sequencing and bulk RNA-sequencing (P < 0.05). Gene set enrichment analysis (GSEA) analysis identified six potential biological pathways of AFF3 involved in RC. As for the potential mechanism of AFF3 in RC, we concluded in this article that AFF3 eQTL could negatively modulate the levels of the X-11,315 metabolite (IVW method; OR = 0.9127; 95% CI = 0.8530-0.9765; P = 0.0081; heterogeneity = 0.4150; pleiotropy = 0.8852), exhibiting preventive effects against RC risks (IVW method; OR = 0.9987; 95% CI = 0.9975-0.9999; P = 0.0380; heterogeneity = 0.5362; pleiotropy = 0.9808).\nCONCLUSIONS: We concluded that AFF3 could serve as a novel eQTL-mediated susceptibility gene in RC and reveal its potential mechanism of elevating RC risks via negatively regulating the X-11,315 metabolite levels.", "claims": [{"id": "claim-method", "statement": "Two-sample MR analyses were applied in this article to infer causal relationships between modifiable exposures and disease outcomes through the “TwoSampleMR” R package [23]. During the analysis, the inverse variance weighted (IVW) approach was deemed the main outcome of this study, compared with the others (the MR Egger method, the weighted median method, the weighted mode method, and the simple mode method) [24].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38886730", "locator": "sections[6] \"MR analysis and sensitivity analyses\" paragraph 2", "quote": "Two-sample MR analyses were applied in this article to infer causal relationships between modifiable exposures and disease outcomes through the “TwoSampleMR” R package [23]. During the analysis, the inverse variance weighted (IVW) approach was deemed the main outcome of this study, compared with the others (the MR Egger method, the weighted median method, the weighted mode method, and the simple mode method) [24]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "eQTLs or RC genetic data were obtained from the online IEU OpenGWAS project website (https://gwas.mrcieu.ac.uk/), with GWAS IDs of eqtl-a-Ensembl IDs or ukb-b-1316. 1,400 metabolite genetic data were obtained from the online GWAS Catalog website (https://www.ebi.ac.uk/gwas/), with the IDs GCST90199621 to GCST90201020. The cis-eQTLs genetic data were obtained from the eQTLGen online website (https://www.eqtlgen.org/cis-eqtls.html). ScRNA-sequencing and bulk RNA-sequencing data were obtained from the TCGA-KIRC, the ICGC-RC, and the GSE159115 datasets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38886730", "locator": "sections[22] \"Data availability\" paragraph 2", "quote": "eQTLs or RC genetic data were obtained from the online IEU OpenGWAS project website (https://gwas.mrcieu.ac.uk/), with GWAS IDs of eqtl-a-Ensembl IDs or ukb-b-1316. 1,400 metabolite genetic data were obtained from the online GWAS Catalog website (https://www.ebi.ac.uk/gwas/), with the IDs GCST90199621 to GCST90201020. The cis-eQTLs genetic data were obtained from the eQTLGen online website (https://www.eqtlgen.org/cis-eqtls.html). ScRNA-sequencing and bulk RNA-sequencing data were obtained from the TCGA-KIRC, the ICGC-RC, and the GSE159115 datasets."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Our results provided the first evidence for AFF3 eQTL elevating RC risks, suggesting its oncogenic roles (IVW method; odds ratio (OR) = 1.0005; 95% confidence interval (CI) = 1.0001–1.0010; P = 0.0285; heterogeneity = 0.9588; pleiotropy = 0.8397).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Our results provided the first evidence for AFF3 eQTL elevating RC risks, suggesting its oncogenic roles (IVW method; odds ratio (OR) = 1.0005; 95% confidence interval (CI) = 1.0001–1.0010; P = 0.0285; heterogeneity = 0.9588; pleiotropy = 0.8397)."}, "evidence": [{"asset": "source:pmid:38886730", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Our results provided the first evidence for AFF3 eQTL elevating RC risks, suggesting its oncogenic roles (IVW method; odds ratio (OR) = 1.0005; 95% confidence interval (CI) = 1.0001–1.0010; P = 0.0285; heterogeneity = 0.9588; pleiotropy = 0.8397)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Our results provided the first evidence for AFF3 eQTL elevating RC risks, suggesting its oncogenic roles (IVW method; odds ratio (OR) = 1.0005; 95% confidence interval (CI) = 1.0001–1.0010; P = 0.0285; heterogeneity = 0.9588; pleiotropy = 0.8397).", "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:38886730"], "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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