Metabolites and coronary heart disease: A two sample Mendelian randomization
Background: In observational studies, circulating metabolites were related to Coronary heart disease (CHD), but their causal relationship is unknown. In this study, we sought to determine a bidirectional causal relationship between circulating metabolites and CHD and to explore whether circulating m...
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Elsevier
2025-09-01
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| Series: | International Journal of Cardiology. Cardiovascular Risk and Prevention |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772487525000030 |
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| author | Yang Sheng Feng Gao Zhenyu Zhu Tianjie Zhang Wei Zhang |
| author_facet | Yang Sheng Feng Gao Zhenyu Zhu Tianjie Zhang Wei Zhang |
| author_sort | Yang Sheng |
| collection | DOAJ |
| description | Background: In observational studies, circulating metabolites were related to Coronary heart disease (CHD), but their causal relationship is unknown. In this study, we sought to determine a bidirectional causal relationship between circulating metabolites and CHD and to explore whether circulating metabolites are associated with a decreased risk of CHD. Methods: In our two-sample Mendelian randomization (MR) study, the top SNPs associated with circulating metabolites (n = 24, 925) as well as CHD (n = 86, 995) were acquired from publicly available genome-wide association studies (GWAS). The SNPs estimates were pooled using inverse variance weighted meta-analysis, with median weighted by sensitivity analyses, MR Egger and MR Pleiotropy Residual Sum and Outlier (PRESSO). Results: Free cholesterol in large LDL(p, 6.9E-07; OR, 2.2; 95%CI,1.6–3.0),total cholesterol in medium LDL(p, 1.0E-06; OR, 1.8; 95%CI,1.4–2.3)Total cholesterol in LDL (p,1.43083E-05; OR,1.7; 95%CI, 1.3–2.2). Phospholipids in medium LDL (p,0.0; OR,1.6; 95%CI, 1.2–2.1); Total cholesterol in small VLDL (p,0.0; OR, 1.8; 95%CI, 1.2–2.7); Triglycerides in small VLDL (p,0.0, OR, 1.3; 95%CI, 1.0–1.6); Free cholesterol in small VLDL (p,0.0; OR,1.3; 95%CI, 1.0–1.7); Phospholipids in small VLDL (p,0.0; OR,1.3, 95%CI,1.0–1.7); Triglycerides in small HDL (p,0.0, OR,1.3,95%CI,1.0–1.7); Alanine (0.0, OR,1.2,95%CI,1.0–1.6) were positively associated with CHD. Phospholipids in medium HDL (p,0.0, OR,0.8; 95%CI, 0.6–0.9) might have a protective effect on CHD, which were negatively associated with CHD. Conclusions: Our MR analysis demonstrated a protective effect of Phospholipids in medium HDL, and a potentially anti-protective effect of Free cholesterol in large LDL, Total cholesterol in medium LDL, Total cholesterol in LDL, Phospholipids in medium LDL, Total cholesterol in small VLDL, Triglycerides in small VLDL, Free cholesterol in small VLDL, Phospholipids in small VLDL, Triglycerides in small HDL, Alanine on the pathogenesis of CHD. Additional studies are required to translate the findings into practice. |
| format | Article |
| id | doaj-art-4fcdd90b2e4f4110860bdf91e15e6da7 |
| institution | Kabale University |
| issn | 2772-4875 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
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| series | International Journal of Cardiology. Cardiovascular Risk and Prevention |
| spelling | doaj-art-4fcdd90b2e4f4110860bdf91e15e6da72025-08-24T05:15:07ZengElsevierInternational Journal of Cardiology. Cardiovascular Risk and Prevention2772-48752025-09-012620036510.1016/j.ijcrp.2025.200365Metabolites and coronary heart disease: A two sample Mendelian randomizationYang Sheng0Feng Gao1Zhenyu Zhu2Tianjie Zhang3Wei Zhang4Department of Cardiology, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou, Zhejiang, ChinaDepartment of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medical College, 88 Jiefang Road, Hangzhou, Zhejiang, ChinaDepartment of Cardiology, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou, Zhejiang, ChinaDepartment of Cardiology, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou, Zhejiang, ChinaDepartment of Cardiology, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou, Zhejiang, China; Corresponding author.Background: In observational studies, circulating metabolites were related to Coronary heart disease (CHD), but their causal relationship is unknown. In this study, we sought to determine a bidirectional causal relationship between circulating metabolites and CHD and to explore whether circulating metabolites are associated with a decreased risk of CHD. Methods: In our two-sample Mendelian randomization (MR) study, the top SNPs associated with circulating metabolites (n = 24, 925) as well as CHD (n = 86, 995) were acquired from publicly available genome-wide association studies (GWAS). The SNPs estimates were pooled using inverse variance weighted meta-analysis, with median weighted by sensitivity analyses, MR Egger and MR Pleiotropy Residual Sum and Outlier (PRESSO). Results: Free cholesterol in large LDL(p, 6.9E-07; OR, 2.2; 95%CI,1.6–3.0),total cholesterol in medium LDL(p, 1.0E-06; OR, 1.8; 95%CI,1.4–2.3)Total cholesterol in LDL (p,1.43083E-05; OR,1.7; 95%CI, 1.3–2.2). Phospholipids in medium LDL (p,0.0; OR,1.6; 95%CI, 1.2–2.1); Total cholesterol in small VLDL (p,0.0; OR, 1.8; 95%CI, 1.2–2.7); Triglycerides in small VLDL (p,0.0, OR, 1.3; 95%CI, 1.0–1.6); Free cholesterol in small VLDL (p,0.0; OR,1.3; 95%CI, 1.0–1.7); Phospholipids in small VLDL (p,0.0; OR,1.3, 95%CI,1.0–1.7); Triglycerides in small HDL (p,0.0, OR,1.3,95%CI,1.0–1.7); Alanine (0.0, OR,1.2,95%CI,1.0–1.6) were positively associated with CHD. Phospholipids in medium HDL (p,0.0, OR,0.8; 95%CI, 0.6–0.9) might have a protective effect on CHD, which were negatively associated with CHD. Conclusions: Our MR analysis demonstrated a protective effect of Phospholipids in medium HDL, and a potentially anti-protective effect of Free cholesterol in large LDL, Total cholesterol in medium LDL, Total cholesterol in LDL, Phospholipids in medium LDL, Total cholesterol in small VLDL, Triglycerides in small VLDL, Free cholesterol in small VLDL, Phospholipids in small VLDL, Triglycerides in small HDL, Alanine on the pathogenesis of CHD. Additional studies are required to translate the findings into practice.http://www.sciencedirect.com/science/article/pii/S2772487525000030MetabolitesCoronary heart diseaseMendelian randomization |
| spellingShingle | Yang Sheng Feng Gao Zhenyu Zhu Tianjie Zhang Wei Zhang Metabolites and coronary heart disease: A two sample Mendelian randomization International Journal of Cardiology. Cardiovascular Risk and Prevention Metabolites Coronary heart disease Mendelian randomization |
| title | Metabolites and coronary heart disease: A two sample Mendelian randomization |
| title_full | Metabolites and coronary heart disease: A two sample Mendelian randomization |
| title_fullStr | Metabolites and coronary heart disease: A two sample Mendelian randomization |
| title_full_unstemmed | Metabolites and coronary heart disease: A two sample Mendelian randomization |
| title_short | Metabolites and coronary heart disease: A two sample Mendelian randomization |
| title_sort | metabolites and coronary heart disease a two sample mendelian randomization |
| topic | Metabolites Coronary heart disease Mendelian randomization |
| url | http://www.sciencedirect.com/science/article/pii/S2772487525000030 |
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