Identification and Mendelian randomization validation of pathogenic gene biomarkers in obstructive sleep apnea.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39220737", "kind": "science-record", "revision": 2, "content_hash": "sha256:80754ff458c160aac50220f28230fdf8f37deea054bc83628c298da0fb82242a", "created_at": "2026-11-01T20:29:21Z", "updated_at": "2026-11-01T21:33:48Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and Mendelian randomization validation of pathogenic gene biomarkers in obstructive sleep apnea.", "doi": "10.3389/fneur.2024.1442835", "pmid": "39220737", "authors": ["Nianjin Gong", "Yu Tuo", "Peijun Liu"], "journal": "Frontiers in neurology", "year": 2024, "abstract": "Background: By 2020, obstructive sleep apnea (OSA), a prevalent respiratory disorder, had affected 26.6-43.2% of males and 8.7-27.8% of females worldwide. OSA is associated with conditions such as hypertension, diabetes, and tumor progression; however, the precise underlying pathways remain elusive. This study aims to identify genetic markers and molecular mechanisms of OSA to improve understanding and treatment strategies.\nMethods: The GSE135917 dataset related to OSA was obtained from the GEO database. Differentially expressed genes (DEGs) were subsequently identified. Weighted gene co-expression network analysis (WGCNA) was conducted to pinpoint disease-associated genes. The intersection of these data enabled the identification of potential diagnostic DEGs. Further analyses included Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment studies, exploration of protein-protein interactions based on these genes, and an examination of immune infiltration. Mendelian randomization was employed to validate core genes against the Genome-Wide Association Study database.\nResults: A total of 194 DEGs were identified in this study. WGCNA network analysis highlighted 2,502 DEGs associated with OSA. By intersecting these datasets, 53 diagnostic DEGs primarily involved in metabolic pathways were identified. Significant alterations were observed in immune cell populations, including memory B cells, plasma cells, naive CD4 T cells, M0 macrophages, and activated dendritic cells. CETN3, EEF1E1, PMM2, GTF2A2, and RRM2 emerged as hub genes implicated in the pathogenesis. A line graph model provides diagnostic insights. Mendelian randomization analysis confirmed a causal link between CETN3 and GTF2A2 with OSA.\nConclusion: Through WGCNA, this analysis uncovered significant genetic foundations of OSA, identifying 2,502 DEGs and 194 genes associated with the disorder. Among these, CETN3 and GTF2A2 were found to have causal relationships with OSA.", "claims": [{"id": "claim-method", "statement": "Utilizing the WGCNA approach, the normalized expression data were analyzed.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39220737", "locator": "sections[4] \"WGCNA analysis of gene expression\" paragraph 2", "quote": "Utilizing the WGCNA approach, the normalized expression data were analyzed."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39220737", "locator": "sections[21] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Through WGCNA, the analysis identified 2,502 DEGs and 194 genes associated with OSA, with CETN3 and GTF2A2 found to have causal relationships with OSA.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39220737", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Through WGCNA, this analysis uncovered significant genetic foundations of OSA, identifying 2,502 DEGs and 194 genes associated with the disorder. Among these, CETN3 and GTF2A2 were found to have causal relationships with OSA."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Through WGCNA, the analysis identified 2,502 DEGs and 194 genes associated with OSA, with CETN3 and GTF2A2 found to have causal relationships with OSA.", "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:39220737"], "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:GSE135917"], "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:GSE135917"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39220737", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fneur.2024.1442835", "sha256": "sha256:256d8fbaac9dd66617fbd887ac7711c75d2c218876228420a687b493de7d884b", "bytes": 41686, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fneur.2024.1442835", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11363542", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE135917", "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=GSE135917", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE135917", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4037879", "GSM4037880", "GSM4037881", "GSM4037882", "GSM4037883", "GSM4037884", "GSM4037885", "GSM4037886", "GSM4037887", "GSM4037888", "GSM4037889", "GSM4037890", "GSM4037891", "GSM4037892", "GSM4037893", "GSM4037894", "GSM4037895", "GSM4037896", "GSM4037897", "GSM4037898", "GSM4037899", "GSM4037900", "GSM4037901", "GSM4037902", "GSM4037903", "GSM4037904", "GSM4037905", "GSM4037906", "GSM4037907", "GSM4037908", "GSM4037909", "GSM4037910", "GSM4037911", "GSM4037912", "GSM4037913", "GSM4037914", "GSM4037915", "GSM4037916", "GSM4037917", "GSM4037918", "GSM4037919", "GSM4037920", "GSM4037921", "GSM4037922", "GSM4037923", "GSM4037924", "GSM4037925", "GSM4037926", "GSM4037927", "GSM4037928", "GSM4037929", "GSM4037930", "GSM4037931", "GSM4037932", "GSM4037933", "GSM4037934", "GSM4037935", "GSM4037936", "GSM4037937", "GSM4037938", "GSM4037939", "GSM4037940", "GSM4037941", "GSM4037942", "GSM4037943", "GSM4037944"], "sample_count": 66, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Subcutaneous fat transcriptome in obstructive sleep apnea and after treatment with CPAP", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE135917 not downloaded", "asset:data:geo:GSE135917 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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 Study"}}, {"id": "method-2", "family": "genetic_association", "specific": "mendelian_randomisation", "label": "Genetic association (GWAS / linkage / MR)", "dsl_operations": ["mr_estimate"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["genotype_phenotype_table"], "evidence": {"score": 0.7, "band": "medium", "quote": "Mendelian randomization"}}, {"id": "method-3", "family": null, "specific": null, "label": "Weighted gene co-expression network analysis (WGCNA)", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Utilizing the WGCNA approach, the normalized expression data were analyzed."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": true, "required_operations": ["gwas_locus_scan"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: gwas."}, "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": ["GSE135917"], "resolved_accessions": ["GSE135917"], "statements": ["The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author."], "basis": "The paper names GSE135917 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["gwas_locus_scan"], "assets": ["source:pmid:39220737", "data:geo:GSE135917"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE135917"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:29:59Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11862, "completion_tokens": 1290, "cached_tokens": 264}}, "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:39220737", "type": "paper", "label": "pmid:39220737"}, {"id": "source:pmid:39220737", "type": "manuscript", "label": "PMID 39220737 full text"}, {"id": "data:geo:GSE135917", "type": "dataset", "label": "GEO GSE135917"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:39220737", "type": "paper", "label": "pmid:39220737"}, {"id": "source:pmid:39220737", "type": "manuscript", "label": "PMID 39220737 full text"}, {"id": "data:geo:GSE135917", "type": "dataset", "label": "GEO GSE135917"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39220737", "type": "extraction", "used": ["source:pmid:39220737"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE135917", "type": "accession_resolution", "used": ["data:geo:GSE135917"], "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:39220737", "parent_hash": "sha256:d0b8bb3aac59eb2bfc821a56eefecb0dfbcdc2eb8b7074036f29395205b62a39", "fork_of": null, "generation": 1}, "gaps": ["asset:data:geo:GSE135917 licence not read", "asset:data:geo:GSE135917 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "genetic_association", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["gwas_locus_scan"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["Genome-Wide Association Study"], "order_basis": "analysis_only", "id": "assay:1"}]}