PD-1/PD-L1 and coronary heart disease: a mendelian randomization study.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39494235", "kind": "science-record", "revision": 2, "content_hash": "sha256:1b7ce8776cb95703ccfe44fa5c34396e7b11ebe808a281afd950b0c306806b6b", "created_at": "2026-11-01T20:29:44Z", "updated_at": "2026-11-01T21:34:15Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "PD-1/PD-L1 and coronary heart disease: a mendelian randomization study.", "doi": "10.3389/fcvm.2024.1424770", "pmid": "39494235", "authors": ["Liangjia Zeng", "Yinglan Liang", "Ruoyun Zhou", "Wenting Yang", "Kexin Chen", "Baixin He", "Yuqing Qiu", "Linglong Liu", "Deyang Zhou", "Zhaolin Xiao", "Haowen Liang", "Binghua Zhang", "Renyu Li", "Lihong Yu", "Min Yi", "Xiaozhen Lin"], "journal": "Frontiers in cardiovascular medicine", "year": 2024, "abstract": "Introduction: It has been found that programmed cell death protein-1 (PD-1) or its ligand PD-L1 may play an important role in the onset and progression of coronary heart disease (CHD). Thus, we conducted this mendelian randomization analysis (MR) to estimate the causal relationship between PD-1/PD-L1 and 5 specific CHDs (chronic ischemic heart disease, acute myocardial infarction, angina pectoris, coronary atherosclerosis, and unstable angina pectoris), complemented by gene set enrichment analysis (GSEA) for further validation.\nMethods: Publicly available summary-level data were attained from the UK Biobank with genetic instruments obtained from the largest available, nonoverlapping genome-wide association studies (GWAS). Our analysis involved various approaches including inverse variance-weighted meta-analysis, alternative techniques like weighted median, MR-Egger, MR-multipotency residuals and outliers detection (PRESSO), along with multiple sensitivity assessments such as MR-Egger intercept test, Cochran's Q test, and leave-one-out sensitivity analysis to evaluate and exclude any anomalies.\nResults: Gene expression profile (GSE71226) was obtained from Gene Expression Omnibus (GEO) database for GSEA. IVW analysis showed a causal association between PD-1 and chronic ischemic heart disease (OR, 0.997; 95%CI, 0.995-0.999; P, 0.009), chronic ischemic heart disease and PD-1 (beta, -3.1; 95%CI, -6.017 to -0.183; P, 0.037), chronic ischemic heart disease and PD-L1 (beta, -3.269; 95%CI, -6.197 to -0.341; P, 0.029). No significant causal relationship was found between PD-1/PD-L1 and other 4 CHDs. The accuracy and robustness of these findings were confirmed by sensitivity tests. GSEA found that the KEGG pathway and related core genes of \"PD-L1 expression and PD-1 checkpoint pathway in cancer\" pathway were downregulated in CHD.\nDiscussion: This study provided evidence of a bidirectional causal relationship between PD-1 and chronic ischemic heart disease and a protective association between chronic ischemic heart disease and PD-L1.", "claims": [{"id": "claim-method", "statement": "Inverse-variance weight (IVW) were the principal analyses for our study as it is the most efficient analysis method with valid instrumental variables, accounting for heterogeneity in the variant-specific casual estimates.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39494235", "locator": "sections[10] \"Univariable MR\" paragraph 2", "quote": "Inverse-variance weight (IVW) were the principal analyses for our study as it is the most efficient analysis method with valid instrumental variables, accounting for heterogeneity in the variant-specific casual estimates."}], "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 authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39494235", "locator": "sections[23] \"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 authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "IVW analysis showed a causal association between PD-1 and chronic ischemic heart disease (OR, 0.997; 95%CI, 0.995-0.999; P, 0.009), chronic ischemic heart disease and PD-1 (beta, −3.1; 95%CI, −6.017 to −0.183; P, 0.037), chronic ischemic heart disease and PD-L1 (beta, −3.269; 95%CI, −6.197 to −0.341; P, 0.029).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "IVW analysis showed a causal association between PD-1 and chronic ischemic heart disease (OR, 0.997; 95%CI, 0.995-0.999; P, 0.009), chronic ischemic heart disease and PD-1 (beta, −3.1; 95%CI, −6.017 to −0.183; P, 0.037), chronic ischemic heart disease and PD-L1 (beta, −3.269; 95%CI, −6.197 to −0.341; P, 0.029)."}, "evidence": [{"asset": "source:pmid:39494235", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "IVW analysis showed a causal association between PD-1 and chronic ischemic heart disease (OR, 0.997; 95%CI, 0.995-0.999; P, 0.009), chronic ischemic heart disease and PD-1 (beta, −3.1; 95%CI, −6.017 to −0.183; P, 0.037), chronic ischemic heart disease and PD-L1 (beta, −3.269; 95%CI, −6.197 to −0.341; P, 0.029)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "IVW analysis showed a causal association between PD-1 and chronic ischemic heart disease (OR, 0.997; 95%CI, 0.995-0.999; P, 0.009), chronic ischemic heart disease and PD-1 (beta, −3.1; 95%CI, −6.017 to −0.183; P, 0.037), chronic ischemic heart disease and PD-L1 (beta, −3.269; 95%CI, −6.197 to −0.341; P, 0.029).", "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:39494235"], "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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