Causal relationships between serum metabolites and coronary heart disease risk: a mendelian randomization study
BackgroundCoronary heart disease (CHD) represents a substantial global burden in terms of morbidity and mortality. Understanding the causal relationships between serum metabolites and CHD can provide a crucial understanding of disease mechanisms and potential therapeutic targets.MethodsWe conducted...
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Frontiers Media S.A.
2025-03-01
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| author | Xiao-Yan Meng Xiao-Yan Meng Yong-Qing Zhu Yong-Qing Zhu Ying-Jie Zhang Ying-Jie Zhang Wei Sun Shu-Ang Li |
| author_facet | Xiao-Yan Meng Xiao-Yan Meng Yong-Qing Zhu Yong-Qing Zhu Ying-Jie Zhang Ying-Jie Zhang Wei Sun Shu-Ang Li |
| author_sort | Xiao-Yan Meng |
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| description | BackgroundCoronary heart disease (CHD) represents a substantial global burden in terms of morbidity and mortality. Understanding the causal relationships between serum metabolites and CHD can provide a crucial understanding of disease mechanisms and potential therapeutic targets.MethodsWe conducted a Mendelian randomization (MR) approach to explore the potential causal associations between serum metabolites and CHD risk. The primary analysis employed the inverse variance weighted (IVW) method, supplemented by additional analyses, including MR-Egger, weighted median, weighted mode, and sample mode. To bolster the robustness and reliability of our findings, we performed sensitivity analyses, which included evaluating, horizontal pleiotropy and leave-one-out analysis. Additionally, pathway enrichment analysis was conducted.ResultsWe identified 15 known and 11 unknown metabolites with potential associations to CHD. Among the known, six displayed protective effects, while nine were identified as risk factors. Notably, many of these metabolites are closely related to mitochondrial function, which was further supported by pathways and enrichment analysis. Using multiple statistical models to ensure robust results, we unveiled a significant association between hexadecanedioate, a palmitoyl lipid metabolized in mitochondria, and a ∼18% reduced risk of CHD (OR = 0.82, 95%CI: 0.72–0.93).ConclusionMR analysis revealed 6 protective molecules, 9 hazardous metabolites associated with CHD. Many of these known metabolites are closely link to mitochondrial function, suggesting a critical role of mitochondria in CHD development. In particular, hexadecanedioate, an essential component for mitochondrial energy production, was inversely associated with CHD risk. This suggests that mitochondrial function, and specifically the role of hexadecanedioate, may be pivotal in the development and progression of CHD. |
| format | Article |
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| institution | DOAJ |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj-art-b7d784491009483eaf7ecc9ff7e1028f2025-08-20T02:50:47ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-03-011610.3389/fgene.2025.14403641440364Causal relationships between serum metabolites and coronary heart disease risk: a mendelian randomization studyXiao-Yan Meng0Xiao-Yan Meng1Yong-Qing Zhu2Yong-Qing Zhu3Ying-Jie Zhang4Ying-Jie Zhang5Wei Sun6Shu-Ang Li7Clinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaThe Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaClinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaThe Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaClinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaThe Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaDepartment of Burn and Repair Reconstruction, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaClinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaBackgroundCoronary heart disease (CHD) represents a substantial global burden in terms of morbidity and mortality. Understanding the causal relationships between serum metabolites and CHD can provide a crucial understanding of disease mechanisms and potential therapeutic targets.MethodsWe conducted a Mendelian randomization (MR) approach to explore the potential causal associations between serum metabolites and CHD risk. The primary analysis employed the inverse variance weighted (IVW) method, supplemented by additional analyses, including MR-Egger, weighted median, weighted mode, and sample mode. To bolster the robustness and reliability of our findings, we performed sensitivity analyses, which included evaluating, horizontal pleiotropy and leave-one-out analysis. Additionally, pathway enrichment analysis was conducted.ResultsWe identified 15 known and 11 unknown metabolites with potential associations to CHD. Among the known, six displayed protective effects, while nine were identified as risk factors. Notably, many of these metabolites are closely related to mitochondrial function, which was further supported by pathways and enrichment analysis. Using multiple statistical models to ensure robust results, we unveiled a significant association between hexadecanedioate, a palmitoyl lipid metabolized in mitochondria, and a ∼18% reduced risk of CHD (OR = 0.82, 95%CI: 0.72–0.93).ConclusionMR analysis revealed 6 protective molecules, 9 hazardous metabolites associated with CHD. Many of these known metabolites are closely link to mitochondrial function, suggesting a critical role of mitochondria in CHD development. In particular, hexadecanedioate, an essential component for mitochondrial energy production, was inversely associated with CHD risk. This suggests that mitochondrial function, and specifically the role of hexadecanedioate, may be pivotal in the development and progression of CHD.https://www.frontiersin.org/articles/10.3389/fgene.2025.1440364/fullcoronary heart diseaseserum metabolitesmendelian randomizationcausal relationshiphexadecanedioaterisk factors |
| spellingShingle | Xiao-Yan Meng Xiao-Yan Meng Yong-Qing Zhu Yong-Qing Zhu Ying-Jie Zhang Ying-Jie Zhang Wei Sun Shu-Ang Li Causal relationships between serum metabolites and coronary heart disease risk: a mendelian randomization study Frontiers in Genetics coronary heart disease serum metabolites mendelian randomization causal relationship hexadecanedioate risk factors |
| title | Causal relationships between serum metabolites and coronary heart disease risk: a mendelian randomization study |
| title_full | Causal relationships between serum metabolites and coronary heart disease risk: a mendelian randomization study |
| title_fullStr | Causal relationships between serum metabolites and coronary heart disease risk: a mendelian randomization study |
| title_full_unstemmed | Causal relationships between serum metabolites and coronary heart disease risk: a mendelian randomization study |
| title_short | Causal relationships between serum metabolites and coronary heart disease risk: a mendelian randomization study |
| title_sort | causal relationships between serum metabolites and coronary heart disease risk a mendelian randomization study |
| topic | coronary heart disease serum metabolites mendelian randomization causal relationship hexadecanedioate risk factors |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2025.1440364/full |
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