Transcriptome-wide association study identifies new susceptibility genes for degenerative cervical spondylosis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36660900", "kind": "science-record", "revision": 2, "content_hash": "sha256:cca53f10ab5ae19a203ddb22fc85320ec4f759eb836f4a5c277d419d11896fc5", "created_at": "2026-11-01T19:01:13Z", "updated_at": "2026-11-01T21:29:55Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Transcriptome-wide association study identifies new susceptibility genes for degenerative cervical spondylosis.", "doi": "10.1302/2046-3758.121.BJR-2022-0225.R1", "pmid": "36660900", "authors": ["Jiawen Xu", "Haibo Si", "Yi Zeng", "Yuangang Wu", "Shaoyun Zhang", "Yuan Liu", "Mingyang Li", "Bin Shen"], "journal": "Bone & joint research", "year": 2023, "abstract": "AIMS: Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive.\nMETHODS: Predicted whole-blood and skeletal muscle gene expression and genome-wide association study (GWAS) data from a DCS database were integrated, and functional summary-based imputation (FUSION) software was used on the integrated data. A transcriptome-wide association study (TWAS) was conducted using FUSION software to assess the association between predicted gene expression and DCS risk. The TWAS-identified genes were verified via comparison with differentially expressed genes (DEGs) in DCS RNA expression profiles in the Gene Expression Omnibus (GEO) (Accession Number: GSE153761). The Functional Mapping and Annotation (FUMA) tool for genome-wide association studies and Meta tools were used for gene functional enrichment and annotation analysis.\nRESULTS: The TWAS detected 420 DCS genes with p < 0.05 in skeletal muscle, such as ribosomal protein S15A (RPS15A) (PTWAS = 0.001), and 110 genes in whole blood, such as selectin L (SELL) (PTWAS = 0.001). Comparison with the DCS RNA expression profile identified 12 common genes, including Apelin Receptor (APLNR) (PTWAS = 0.001, PDEG = 0.025). In total, 148 DCS-enriched Gene Ontology (GO) terms were identified, such as mast cell degranulation (GO:0043303); 15 DCS-enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified, such as the sphingolipid signalling pathway (ko04071). Nine terms, such as degradation of the extracellular matrix (R-HSA-1474228), were common to the TWAS enrichment results and the RNA expression profile.\nCONCLUSION: Our results identify putative susceptibility genes; these findings provide new ideas for exploration of the genetic mechanism of DCS development and new targets for preclinical intervention and clinical treatment.Cite this article: Bone Joint Res 2023;12(1):80-90.", "claims": [{"id": "claim-method", "statement": "The TWAS of DCS was carried out by using functional summary-based imputation (FUSION) software.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36660900", "locator": "sections[7] \"TWAS of DCS\" paragraph 2", "quote": "The TWAS of DCS was carried out by using functional summary-based imputation (FUSION) software."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data sharing The genome-wide association study (GWAS) summary data of degenerative cervical spondylosis (DCS): the UK Biobank (http://geneatlas.roslin.ed.ac.uk/). RNA expression profiles of DCS were acquired from Gene Expression Omnibus (GEO) datasets (GSE153761, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE153761).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36660900", "locator": "sections[16] \"fn-group\" paragraph 1", "quote": "Data sharing The genome-wide association study (GWAS) summary data of degenerative cervical spondylosis (DCS): the UK Biobank (http://geneatlas.roslin.ed.ac.uk/). RNA expression profiles of DCS were acquired from Gene Expression Omnibus (GEO) datasets (GSE153761, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE153761)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "TWAS analysis identified 530 significant genes for DCS with p-values < 0.05.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36660900", "locator": "sections[11] \"TWAS results of DCS\" paragraph 2", "quote": "TWAS analysis identified 530 significant genes for DCS with p-values < 0.05 (Figure 1)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "TWAS analysis identified 530 significant genes for DCS with p-values < 0.05.", "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:36660900"], "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:GSE153761"], "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:GSE153761"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36660900", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1302/2046-3758.121.BJR-2022-0225.R1", "sha256": "sha256:4c84cab9617c7ec574dcdd479dd221771e11adbcbc412cc4ff0e88676d5ca258", "bytes": 29782, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1302/2046-3758.121.BJR-2022-0225.R1", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9872045", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE153761", "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=GSE153761", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE153761", "version": null, "note": "Data sharing The genome-wide association study (GWAS) summary data of degenerative cervical spondylosis (DCS): the UK Biobank (http://geneatlas.roslin.ed.ac.uk/). 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