A Cross-Tissue Transcriptome-Wide Association Study Identifies Novel Susceptibility Genes for Juvenile Idiopathic Arthritis in Asia and Europe.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35967305", "kind": "science-record", "revision": 4, "content_hash": "sha256:4c5639f41e823b1d8c39478227112c821dcfd79eee5dad9c0d99153b0557786e", "created_at": "2026-11-01T18:15:05Z", "updated_at": "2026-11-01T22:07:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A Cross-Tissue Transcriptome-Wide Association Study Identifies Novel Susceptibility Genes for Juvenile Idiopathic Arthritis in Asia and Europe.", "doi": "10.3389/fimmu.2022.941398", "pmid": "35967305", "authors": ["Jiawen Xu", "Jun Ma", "Yi Zeng", "Haibo Si", "Yuangang Wu", "Shaoyun Zhang", "Bin Shen"], "journal": "Frontiers in immunology", "year": 2022, "abstract": "Background: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children, and its pathogenesis is still unclear. Genome-wide association studies (GWASs) of JIA have identified hundreds of risk factors, but few of them implicated specific biological mechanisms.\nMethods: A cross-tissue transcriptome-wide association study (TWAS) was performed with the functional summary-based imputation software (FUSION) tool based on GWAS summary datasets (898 JIA patients and 346,102 controls from BioBank Japan (BBJ)/FinnGen). The gene expression reference weights of skeletal muscle and the whole blood were obtained from the Genotype-Tissue Expression (GTExv8) project. JIA-related genes identified by TWAS findings genes were further compared with the differentially expressed genes (DEGs) identified by the mRNA expression profile of JIA from the Gene Expression Omnibus (GEO) database (accession number: GSE1402). Last, candidate genes were analyzed using functional enrichment and annotation analysis by Metascape to examine JIA-related gene sets.\nResults: The TWAS identified 535 significant genes with P < 0.05 and contains 350 for Asian and 195 for European (including 10 genes both expressed in Asian and European), such as CDC16 (P = 1.72E-03) and PSMD5-AS1 (P = 3.65E-02). Eight overlapping genes were identified based on TWAS results and DEGs of JIA patients, such as SIRPB1 (PTWAS = 4.21E-03, PDEG = 1.50E-04) and FRAT2 (PTWAS = 2.82E-02, PDEG = 1.43E-02). Pathway enrichment analysis of TWAS identified 183 pathways such as cytokine signaling in the immune system and cell adhesion molecules. By integrating the results of DEGs pathway and process enrichment analyses, 19 terms were identified such as positive regulation of T-cell activation.\nConclusion: By conducting two populations TWAS, we identified a group of JIA-associated genes and pathways, which may provide novel clues to uncover the pathogenesis of JIA.", "claims": [{"id": "claim-method", "statement": "Tissue-related TWAS analysis of JIA was carried out by using functional summary-based imputation software (FUSION) via integrating the GWAS summary datasets of JIA and pre-computed gene expression weights reference of skeletal muscle and whole blood.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35967305", "locator": "sections[4] \"Transcriptome-Wide Association Study Analysis of Juvenile Idiopathic Arthritis\" paragraph 2", "quote": "Tissue-related TWAS analysis of JIA was carried out by using functional summary-based imputation software (FUSION) via integrating the GWAS summary datasets of JIA and pre-computed gene expression weights reference of skeletal muscle and whole blood."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35967305", "locator": "sections[15] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material ."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The TWAS identified 535 significant genes with P < 0.05 and contains 350 for Asian and 195 for European (including 10 genes both expressed in Asian and European), such as CDC16 (P = 1.72E-03) and PSMD5-AS1 (P = 3.65E-02).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35967305", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The TWAS identified 535 significant genes with P < 0.05 and contains 350 for Asian and 195 for European (including 10 genes both expressed in Asian and European), such as CDC16 (P = 1.72E-03) and PSMD5-AS1 (P = 3.65E-02)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The TWAS identified 535 significant genes with P < 0.05 and contains 350 for Asian and 195 for European (including 10 genes both expressed in Asian and European), such as CDC16 (P = 1.72E-03) and PSMD5-AS1 (P = 3.65E-02).", "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:35967305"], "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:GSE1402"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:regression_modelling_mixed_effects", "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:GSE1402"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:regression_modelling_mixed_effects"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35967305", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2022.941398", "sha256": "sha256:8226516c7b946fc75d4207a5d4c60fd91fa62c3bf01f8d0c539abe652e095095", "bytes": 45844, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2022.941398", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9367689", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE1402", "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=GSE1402", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE1402", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM23159", "GSM23160", "GSM23161", "GSM23162", "GSM23163", "GSM23164", "GSM23165", "GSM23166", "GSM23167", "GSM23168", "GSM23169", "GSM23170", "GSM23171", "GSM23172", "GSM23173", "GSM23174", "GSM23175", "GSM23176", "GSM23177", "GSM23178", "GSM23179", "GSM23180", "GSM23181", "GSM23182", "GSM23183", "GSM23184", "GSM23185", "GSM23186", "GSM23187", "GSM23188", "GSM23189", "GSM23190", "GSM23191", "GSM23192", "GSM23193", "GSM23194", "GSM23195", "GSM23196", "GSM23197", "GSM23198", "GSM23199", "GSM23200", "GSM23201", "GSM23202", "GSM23203", "GSM23204", "GSM23205", "GSM23206", "GSM23207", "GSM23208", "GSM23209", "GSM23210", "GSM23211", "GSM23212", "GSM23213", "GSM23214", "GSM23215"], "sample_count": 57, "group_sizes": null, "group_sizes_basis": null, "platform": "8300", "taxon": "Homo sapiens", "title": "Juvenile Rheumatoid Arthritis Profiles In PBMC and SFMC", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE1402 not downloaded", "asset:data:geo:GSE1402 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "regression_modelling", "specific": "mixed_effects", "label": "Regression modelling", "dsl_operations": [], "missing_operations": ["regression_modelling_mixed_effects"], "expressible": false, "parameters": {}, "data_shapes": ["predictors_and_outcome"], "evidence": {"score": 0.8, "band": "high", "quote": "mixed model"}}, {"id": "method-2", "family": "clustering", "specific": "hierarchical", "label": "Clustering", "dsl_operations": ["hierarchical_cluster"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "hierarchical clustering"}}, {"id": "method-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "Pathway enrichment"}}, {"id": "method-4", "family": "genetic_association", "specific": "gwas", "label": "Genetic association (GWAS / linkage / MR)", "dsl_operations": ["gwas_locus_scan"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["genotype_phenotype_table"], "evidence": {"score": 0.7, "band": "medium", "quote": "Genome-wide association studies"}}, {"id": "method-5", "family": null, "specific": null, "label": "Transcriptome-wide association study (TWAS) using FUSION", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Tissue-related TWAS analysis of JIA was carried out by using functional summary-based imputation software (FUSION) via integrating the GWAS summary datasets of JIA and pre-computed gene expression weights reference of skeletal muscle and whole blood."}}], "targets": [], "gaps": ["method.reader_named_unmapped", "method.regression_modelling_mixed_effects"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": false, "required_operations": [], "missing_operations": ["regression_modelling_mixed_effects"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: mixed_effects."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE1402"], "resolved_accessions": ["GSE1402"], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material ."], "basis": "The paper names GSE1402 in Gene Expression Omnibus (GEO) Datasets and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:35967305", "data:geo:GSE1402"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "regression_modelling_mixed_effects", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE1402"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:59:55Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13958, "completion_tokens": 1360, "cached_tokens": 128}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:35967305", "type": "paper", "label": "pmid:35967305"}, {"id": "source:pmid:35967305", "type": "manuscript", "label": "PMID 35967305 full text"}, {"id": "data:geo:GSE1402", "type": "dataset", "label": "GEO GSE1402"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35967305", "type": "paper", "label": "pmid:35967305"}, {"id": "source:pmid:35967305", "type": "manuscript", "label": "PMID 35967305 full text"}, {"id": "data:geo:GSE1402", "type": "dataset", "label": "GEO GSE1402"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35967305", "type": "extraction", "used": ["source:pmid:35967305"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE1402", "type": "accession_resolution", "used": ["data:geo:GSE1402"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:35967305", "parent_hash": "sha256:d5658d1223842372d6f5838e47b4193f4c9616b7afa27f67a97a9ca7b8515614", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE1402 licence not read", "asset:data:geo:GSE1402 not downloaded", "execution.not_run", "method.reader_named_unmapped", "method.regression_modelling_mixed_effects", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:regression_modelling_mixed_effects"], "assays": [{"role": "analysis", "definition_id": "regression_modelling", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["mixed model"], "order_basis": "analysis_only", "id": "assay:1"}]}