Expression of DDX11 and DNM1L at the 12p11 Locus Modulates Systemic Lupus Erythematosus Susceptibility.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34299244", "kind": "science-record", "revision": 3, "content_hash": "sha256:98d5935acdadceb89928b1c65ccde93703f4dc06cd7c79f9f33bc48e76e73446", "created_at": "2026-11-01T15:41:44Z", "updated_at": "2026-11-01T21:25:50Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Expression of DDX11 and DNM1L at the 12p11 Locus Modulates Systemic Lupus Erythematosus Susceptibility.", "doi": "10.3390/ijms22147624", "pmid": "34299244", "authors": ["Mohammad Saeed", "Alejandro Ibáñez-Costa", "Alejandra María Patiño-Trives", "Laura Muñoz-Barrera", "Eduardo Collantes Estévez", "María Ángeles Aguirre", "Chary López-Pedrera"], "journal": "International journal of molecular sciences", "year": 2021, "abstract": "OBJECTIVES: This study employed genetic and functional analyses using OASIS meta-analysis of multiple existing GWAS and gene-expression datasets to identify novel SLE genes.\nMETHODS: Four hundred and ten genes were mapped using SNIPPER to 30 SLE GWAS loci and investigated for expression in three SLE GEO-datasets and the Cordoba GSE50395-dataset. Blood eQTL for significant SNPs in SLE loci and STRING for functional pathways of differentially expressed genes were used. Confirmatory qPCR on SLE monocytes was performed. The entire 12p11 locus was investigated for genetic association using two additional GWAS. Expression of 150 genes at this locus was assessed. Based on this significance, qPCRs for DNM1L and KRAS were performed.\nRESULTS: Fifty genes were differentially expressed in at least two SLE GEO-datasets, with all probes directionally aligned. DDX11, an RNA helicase involved in genome stability, was downregulated in both GEO and Cordoba datasets. The most significant SNP, rs3741869 in OASIS locus 12p11.21, containing DDX11, was a cis-eQTL regulating DDX11 expression. DDX11 was found repressed. The entire 12p11 locus showed three association peaks. Gene expression in GEO datasets identified DNM1L and KRAS, besides DDX11. Confirmatory qPCR validated DNM1L as an SLE susceptibility gene. DDX11, DNM1L and KRAS interact with each other and multiple known SLE genes including STAT1/STAT4 and major components of IFN-dependent gene expression, and are responsible for signal transduction of cytokines, hormones, and growth-factors, deregulation of which is involved in SLE-development.\nCONCLUSION: A genomic convergence approach with OASIS analysis of multiple GWAS and expression datasets identified DDX11 and DNM1L as novel SLE-genes, the expression of which is altered in monocytes from SLE patients. This study lays the foundation for understanding the pathogenic involvement of DDX11 and DNM1L in SLE by identifying them using a systems-biology approach, while the 12p11 locus harboring these genes was previously missed by four independent GWAS.", "claims": [{"id": "claim-method", "statement": "Significant SNPs in loci harboring differentially expressed genes in SLE were tested using Blood eQTL Browser (expression quantitative trait loci [Available online: https://genenetwork.nl/bloodeqtlbrowser/ (accessed on 10 May 2021)] [22].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34299244", "locator": "sections[11] \"4.2. eQTL and Statistical Analysis\" paragraph 2", "quote": "Significant SNPs in loci harboring differentially expressed genes in SLE were tested using Blood eQTL Browser (expression quantitative trait loci [Available online: https://genenetwork.nl/bloodeqtlbrowser/ (accessed on 10 May 2021)] [22]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data relevant to the study are included in the article or uploaded as Supplementary Materials. All datasets are in publicly available repositories with their accession numbers in the manuscript.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34299244", "locator": "sections[21] \"notes\" paragraph 1", "quote": "All data relevant to the study are included in the article or uploaded as Supplementary Materials. All datasets are in publicly available repositories with their accession numbers in the manuscript."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:34299244"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE10325"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE10325"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34299244", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/ijms22147624", "sha256": "sha256:24d18de9c8ad56ae54d399acabc98a407b355b4ee2ddda6177a59deba2bb9af7", "bytes": 25515, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/ijms22147624", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8304828", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE10325", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10325", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE10325", "version": null, "note": "All data relevant to the study are included in the article or uploaded as Supplementary Materials. 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