PD-1/PD-L1 and coronary heart disease: a mendelian randomization study
IntroductionIt 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...
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Frontiers Media S.A.
2024-10-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| author | Liangjia Zeng Liangjia Zeng Liangjia Zeng Yinglan Liang Yinglan Liang Ruoyun Zhou Ruoyun Zhou Wenting Yang Wenting Yang Kexin Chen Kexin Chen Baixin He Baixin He Yuqing Qiu Yuqing Qiu Linglong Liu Linglong Liu Deyang Zhou Deyang Zhou Zhaolin Xiao Zhaolin Xiao Haowen Liang Haowen Liang Binghua Zhang Binghua Zhang Renyu Li Renyu Li Lihong Yu Min Yi Xiaozhen Lin |
| author_facet | Liangjia Zeng Liangjia Zeng Liangjia Zeng Yinglan Liang Yinglan Liang Ruoyun Zhou Ruoyun Zhou Wenting Yang Wenting Yang Kexin Chen Kexin Chen Baixin He Baixin He Yuqing Qiu Yuqing Qiu Linglong Liu Linglong Liu Deyang Zhou Deyang Zhou Zhaolin Xiao Zhaolin Xiao Haowen Liang Haowen Liang Binghua Zhang Binghua Zhang Renyu Li Renyu Li Lihong Yu Min Yi Xiaozhen Lin |
| author_sort | Liangjia Zeng |
| collection | DOAJ |
| description | IntroductionIt 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.MethodsPublicly 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.ResultsGene 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.DiscussionThis 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. |
| format | Article |
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| institution | OA Journals |
| issn | 2297-055X |
| language | English |
| publishDate | 2024-10-01 |
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| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj-art-fe2011115dc241efbf86f36c04b978a32025-08-20T01:47:50ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2024-10-011110.3389/fcvm.2024.14247701424770PD-1/PD-L1 and coronary heart disease: a mendelian randomization studyLiangjia Zeng0Liangjia Zeng1Liangjia Zeng2Yinglan Liang3Yinglan Liang4Ruoyun Zhou5Ruoyun Zhou6Wenting Yang7Wenting Yang8Kexin Chen9Kexin Chen10Baixin He11Baixin He12Yuqing Qiu13Yuqing Qiu14Linglong Liu15Linglong Liu16Deyang Zhou17Deyang Zhou18Zhaolin Xiao19Zhaolin Xiao20Haowen Liang21Haowen Liang22Binghua Zhang23Binghua Zhang24Renyu Li25Renyu Li26Lihong Yu27Min Yi28Xiaozhen Lin29The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Clinical Medicine, Clinical Medical School, Guangzhou Medical University, Guangzhou, ChinaMedical Exploration and Translation Team, Cardiovascular Medicine and Cardio-Oncology Group, Guangzhou, ChinaMedical Exploration and Translation Team, Cardiovascular Medicine and Cardio-Oncology Group, Guangzhou, ChinaDepartment of Anesthesiology, Clinical Medical School, Guangzhou Medical University, Guangzhou, ChinaDepartment of Clinical Medicine, Clinical Medical School, Guangzhou Medical University, Guangzhou, ChinaMedical Exploration and Translation Team, Cardiovascular Medicine and Cardio-Oncology Group, Guangzhou, ChinaMedical Exploration and Translation Team, Cardiovascular Medicine and Cardio-Oncology Group, Guangzhou, ChinaDepartment of Medical Imageology, Clinical Medical School, Guangzhou Medical University, Guangzhou, ChinaDepartment of Clinical Medicine, Clinical Medical School, Guangzhou Medical University, Guangzhou, ChinaMedical Exploration and Translation Team, Cardiovascular Medicine and Cardio-Oncology Group, Guangzhou, ChinaDepartment of Clinical Medicine, Clinical Medical School, Guangzhou Medical University, Guangzhou, ChinaMedical Exploration and Translation Team, Cardiovascular Medicine and Cardio-Oncology Group, Guangzhou, ChinaDepartment of Clinical Medicine, Clinical Medical School, Guangzhou Medical University, Guangzhou, ChinaMedical Exploration and Translation Team, Cardiovascular Medicine and Cardio-Oncology Group, Guangzhou, ChinaMedical Exploration and Translation Team, Cardiovascular Medicine and Cardio-Oncology Group, Guangzhou, ChinaDepartment of Anesthesiology, Clinical Medical School, Guangzhou Medical University, Guangzhou, ChinaMedical Exploration and Translation Team, Cardiovascular Medicine and Cardio-Oncology Group, Guangzhou, ChinaDepartment of Anesthesiology, Clinical Medical School, Guangzhou Medical University, Guangzhou, ChinaDepartment of Clinical Medicine, Clinical Medical School, Guangzhou Medical University, Guangzhou, ChinaMedical Exploration and Translation Team, Cardiovascular Medicine and Cardio-Oncology Group, Guangzhou, ChinaDepartment of Clinical Medicine, Clinical Medical School, Guangzhou Medical University, Guangzhou, ChinaMedical Exploration and Translation Team, Cardiovascular Medicine and Cardio-Oncology Group, Guangzhou, ChinaDepartment of Clinical Medicine, Clinical Medical School, Guangzhou Medical University, Guangzhou, ChinaMedical Exploration and Translation Team, Cardiovascular Medicine and Cardio-Oncology Group, Guangzhou, ChinaMedical Exploration and Translation Team, Cardiovascular Medicine and Cardio-Oncology Group, Guangzhou, ChinaDepartment of Psychiatry, Clinical Medical School, Guangzhou Medical University, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, ChinaDepartment of Endocrinology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaIntroductionIt 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.MethodsPublicly 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.ResultsGene 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.DiscussionThis 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.https://www.frontiersin.org/articles/10.3389/fcvm.2024.1424770/fullMendelian randomization (MR)coronary heart disease (CHD)PD-1PD-L1GSEA |
| spellingShingle | Liangjia Zeng Liangjia Zeng Liangjia Zeng Yinglan Liang Yinglan Liang Ruoyun Zhou Ruoyun Zhou Wenting Yang Wenting Yang Kexin Chen Kexin Chen Baixin He Baixin He Yuqing Qiu Yuqing Qiu Linglong Liu Linglong Liu Deyang Zhou Deyang Zhou Zhaolin Xiao Zhaolin Xiao Haowen Liang Haowen Liang Binghua Zhang Binghua Zhang Renyu Li Renyu Li Lihong Yu Min Yi Xiaozhen Lin PD-1/PD-L1 and coronary heart disease: a mendelian randomization study Frontiers in Cardiovascular Medicine Mendelian randomization (MR) coronary heart disease (CHD) PD-1 PD-L1 GSEA |
| title | PD-1/PD-L1 and coronary heart disease: a mendelian randomization study |
| title_full | PD-1/PD-L1 and coronary heart disease: a mendelian randomization study |
| title_fullStr | PD-1/PD-L1 and coronary heart disease: a mendelian randomization study |
| title_full_unstemmed | PD-1/PD-L1 and coronary heart disease: a mendelian randomization study |
| title_short | PD-1/PD-L1 and coronary heart disease: a mendelian randomization study |
| title_sort | pd 1 pd l1 and coronary heart disease a mendelian randomization study |
| topic | Mendelian randomization (MR) coronary heart disease (CHD) PD-1 PD-L1 GSEA |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2024.1424770/full |
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