Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan 9:26:200365.
doi: 10.1016/j.ijcrp.2025.200365. eCollection 2025 Sep.

Metabolites and coronary heart disease: A two sample Mendelian randomization

Yang Sheng  1 , Feng Gao  2 , Zhenyu Zhu  1 , Tianjie Zhang  1 , Wei Zhang  1
Affiliations

Metabolites and coronary heart disease: A two sample Mendelian randomization

Yang Sheng et al. Int J Cardiol Cardiovasc Risk Prev. .

Abstract

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.

Keywords: Coronary heart disease; Mendelian randomization; Metabolites.

PubMed Disclaimer

Conflict of interest statement

All authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Three significant assumptions of circulating metabolites on CHD via forward MR.
Fig. 2
Fig. 2
Three significant assumptions of CHD on circulating metabolites via forward MR.
Fig. 3
Fig. 3
Scatter plots for the causal association between circulating metabolites and CHD.
Fig. 4
Fig. 4
Leave-one-out plots for the causal association between circulating metabolites and CHD.
Fig. 5
Fig. 5
Causal relationship of CHD on Triglycerides in small HDL. A. Scatter plots. B. Leave-one-out plots.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Benjamin E.J., et al. Heart disease and stroke statistics-2019 update A report from the American heart association. Circulation. 2019;139:E56–E528. doi: 10.1161/cir.0000000000000659. - DOI - PubMed
    1. Knuuti J., et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur. Heart J. 2020;41:407–477. doi: 10.1093/eurheartj/ehz425. - DOI - PubMed
    1. Zieman S.J., Melenovsky V., Kass D.A. Mechanisms, pathophysiology, and therapy of arterial stiffness. Arterioscler. Thromb. Vasc. Biol. 2005;25:932–943. doi: 10.1161/01.Atv.0000160548.78317.29. - DOI - PubMed
    1. Shah S.H., Newgard C.B. Integrated metabolomics and genomics systems approaches to biomarkers and mechanisms of cardiovascular disease. Circulation-Cardiovascular Genetics. 2015;8:410–419. doi: 10.1161/circgenetics.114.000223. - DOI - PMC - PubMed
    1. Patti G.J., Yanes O., Siuzdak G. Metabolomics: the apogee of the omics trilogy. Nat. Rev. Mol. Cell Biol. 2012;13:263–269. doi: 10.1038/nrm3314. - DOI - PMC - PubMed

LinkOut - more resources