Role of plasma metabolome in mediating the effect of plasma lipidome on NAFLD: a Mendelian randomization study
BackgroundThis study explored the causal connection among the plasma lipidome, nonalcoholic fatty liver disease (NAFLD), and potential metabolome mediators through Mendelian randomization (MR).MethodsWe obtained summary statistics for 179 plasma lipidome traits (N = 7,174), 1,400 plasma metabolome t...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2024.1436827/full |
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| author | Zhuyuan Zheng Shaojie Yang Wanlin Dai Yang Sun Jingnan Wang Xiaolin Zhang Yiming Zheng Jing Kong |
| author_facet | Zhuyuan Zheng Shaojie Yang Wanlin Dai Yang Sun Jingnan Wang Xiaolin Zhang Yiming Zheng Jing Kong |
| author_sort | Zhuyuan Zheng |
| collection | DOAJ |
| description | BackgroundThis study explored the causal connection among the plasma lipidome, nonalcoholic fatty liver disease (NAFLD), and potential metabolome mediators through Mendelian randomization (MR).MethodsWe obtained summary statistics for 179 plasma lipidome traits (N = 7,174), 1,400 plasma metabolome traits (N = 8,299), and one NAFLD trait from publicly available genome-wide association studies. A two-sample MR analysis was conducted to infer causality. Additionally, multiple sensitivity analyses were conducted to assess the heterogeneity, horizontal pleiotropy, and robustness of the MR findings. MetaboAnalyst 6.0 was used for the pathway analysis of the identified lipids and metabolites. Furthermore, we used mediation analysis to assess whether the effect of plasma lipidome on NAFLD was mediated by plasma metabolome.ResultsThe MR analysis predicted a genetically determined causal relationship between plasma lipidomes and NAFLD. No compelling proof was found that genetically predicted NAFLD influenced the risk of the five plasma lipidomes mentioned earlier. Based on established causal relationships between lipids and metabolites, we identified that eight metabolic pathways are closely associated with NAFLD. Our mediation analysis revealed six mediation relationships, indicating the causal pathway from plasma lipids to NAFLD mediated by five specific metabolites. No potential pleiotropy was found in the sensitivity analysis.ConclusionsIn summary, our study identified causal relationships between plasma lipidomes, plasma metabolomes, and NAFLD. Certainly, the impact of plasma lipidomes on NAFLD is not limited to plasma metabolomes, indicating a need to further investigate into other possible mediators. These identified factors may become new biomarkers of the NAFLD contributing to its prevention, diagnosis, and treatment. |
| format | Article |
| id | doaj-art-cec6fa1861374babbf6152a9dcde2948 |
| institution | Kabale University |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Frontiers in Endocrinology |
| spelling | doaj-art-cec6fa1861374babbf6152a9dcde29482025-01-23T05:10:16ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-01-011510.3389/fendo.2024.14368271436827Role of plasma metabolome in mediating the effect of plasma lipidome on NAFLD: a Mendelian randomization studyZhuyuan Zheng0Shaojie Yang1Wanlin Dai2Yang Sun3Jingnan Wang4Xiaolin Zhang5Yiming Zheng6Jing Kong7Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, ChinaBiliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, ChinaInnovation Institute of China Medical University, Shenyang, Liaoning, ChinaBiliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, ChinaBiliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, ChinaBiliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, ChinaBiliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, ChinaBiliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, ChinaBackgroundThis study explored the causal connection among the plasma lipidome, nonalcoholic fatty liver disease (NAFLD), and potential metabolome mediators through Mendelian randomization (MR).MethodsWe obtained summary statistics for 179 plasma lipidome traits (N = 7,174), 1,400 plasma metabolome traits (N = 8,299), and one NAFLD trait from publicly available genome-wide association studies. A two-sample MR analysis was conducted to infer causality. Additionally, multiple sensitivity analyses were conducted to assess the heterogeneity, horizontal pleiotropy, and robustness of the MR findings. MetaboAnalyst 6.0 was used for the pathway analysis of the identified lipids and metabolites. Furthermore, we used mediation analysis to assess whether the effect of plasma lipidome on NAFLD was mediated by plasma metabolome.ResultsThe MR analysis predicted a genetically determined causal relationship between plasma lipidomes and NAFLD. No compelling proof was found that genetically predicted NAFLD influenced the risk of the five plasma lipidomes mentioned earlier. Based on established causal relationships between lipids and metabolites, we identified that eight metabolic pathways are closely associated with NAFLD. Our mediation analysis revealed six mediation relationships, indicating the causal pathway from plasma lipids to NAFLD mediated by five specific metabolites. No potential pleiotropy was found in the sensitivity analysis.ConclusionsIn summary, our study identified causal relationships between plasma lipidomes, plasma metabolomes, and NAFLD. Certainly, the impact of plasma lipidomes on NAFLD is not limited to plasma metabolomes, indicating a need to further investigate into other possible mediators. These identified factors may become new biomarkers of the NAFLD contributing to its prevention, diagnosis, and treatment.https://www.frontiersin.org/articles/10.3389/fendo.2024.1436827/fullMendelian randomization (MR)nonalcoholic fatty liver disease (NAFLD)plasma lipidomeplasma metabolomemediation analysis |
| spellingShingle | Zhuyuan Zheng Shaojie Yang Wanlin Dai Yang Sun Jingnan Wang Xiaolin Zhang Yiming Zheng Jing Kong Role of plasma metabolome in mediating the effect of plasma lipidome on NAFLD: a Mendelian randomization study Frontiers in Endocrinology Mendelian randomization (MR) nonalcoholic fatty liver disease (NAFLD) plasma lipidome plasma metabolome mediation analysis |
| title | Role of plasma metabolome in mediating the effect of plasma lipidome on NAFLD: a Mendelian randomization study |
| title_full | Role of plasma metabolome in mediating the effect of plasma lipidome on NAFLD: a Mendelian randomization study |
| title_fullStr | Role of plasma metabolome in mediating the effect of plasma lipidome on NAFLD: a Mendelian randomization study |
| title_full_unstemmed | Role of plasma metabolome in mediating the effect of plasma lipidome on NAFLD: a Mendelian randomization study |
| title_short | Role of plasma metabolome in mediating the effect of plasma lipidome on NAFLD: a Mendelian randomization study |
| title_sort | role of plasma metabolome in mediating the effect of plasma lipidome on nafld a mendelian randomization study |
| topic | Mendelian randomization (MR) nonalcoholic fatty liver disease (NAFLD) plasma lipidome plasma metabolome mediation analysis |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2024.1436827/full |
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