Causal relationship between human blood metabolites and risk of ischemic stroke: a Mendelian randomization study
Background: Ischemic stroke (IS) is a major cause of death and disability worldwide. Previous studies have reported associations between metabolic disorders and IS. However, evidence regarding the causal relationship between blood metabolites and IS lacking.Methods: A two-sample Mendelian randomizat...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2024.1333454/full |
| _version_ | 1797351649241464832 |
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| author | Menghao He Menghao He Chun Xu Renyi Yang Lijuan Liu Desheng Zhou Siyang Yan |
| author_facet | Menghao He Menghao He Chun Xu Renyi Yang Lijuan Liu Desheng Zhou Siyang Yan |
| author_sort | Menghao He |
| collection | DOAJ |
| description | Background: Ischemic stroke (IS) is a major cause of death and disability worldwide. Previous studies have reported associations between metabolic disorders and IS. However, evidence regarding the causal relationship between blood metabolites and IS lacking.Methods: A two-sample Mendelian randomization analysis (MR) was used to assess the causal relationship between 1,400 serum metabolites and IS. The inverse variance-weighted (IVW) method was employed to estimate the causal effect between exposure and outcome. Additionally, MR-Egger regression, weighted median, simple mode, and weighted mode approaches were employed as supplementary comprehensive evaluations of the causal effects between blood metabolites and IS. Tests for pleiotropy and heterogeneity were conducted.Results: After rigorous selection, 23 known and 5 unknown metabolites were identified to be associated with IS. Among the 23 known metabolites, 13 showed significant causal effects with IS based on 2 MR methods, including 5-acetylamino-6-formylamino-3-methyluracil, 1-ribosyl-imidazoleacetate, Behenoylcarnitine (C22), N-acetyltyrosine, and N-acetylputrescine to (N (1) + N (8))-acetate,these five metabolites were positively associated with increased IS risk. Xanthurenate, Glycosyl-N-tricosanoyl-sphingadienine, Orotate, Bilirubin (E,E), Bilirubin degradation product, C17H18N2O, Bilirubin (Z,Z) to androsterone glucuronide, Bilirubin (Z,Z) to etiocholanolone glucuronide, Biliverdin, and Uridine to pseudouridine ratio were associated with decreased IS risk.Conclusion: Among 1,400 blood metabolites, this study identified 23 known metabolites that are significantly associated with IS risk, with 13 being more prominent. The integration of genomics and metabolomics provides important insights for the screening and prevention of IS. |
| first_indexed | 2024-03-08T13:03:33Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-08T13:03:33Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-b61af27f1bd440bd9eb52949855ab9c42024-01-19T04:29:13ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-01-011510.3389/fgene.2024.13334541333454Causal relationship between human blood metabolites and risk of ischemic stroke: a Mendelian randomization studyMenghao He0Menghao He1Chun Xu2Renyi Yang3Lijuan Liu4Desheng Zhou5Siyang Yan6The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, ChinaHunan University of Chinese Medicine, Changsha, Hunan, ChinaChangde College of Science and Technology, Changde, Hunan, ChinaHunan University of Chinese Medicine, Changsha, Hunan, ChinaThe First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, ChinaThe First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, ChinaThe First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, ChinaBackground: Ischemic stroke (IS) is a major cause of death and disability worldwide. Previous studies have reported associations between metabolic disorders and IS. However, evidence regarding the causal relationship between blood metabolites and IS lacking.Methods: A two-sample Mendelian randomization analysis (MR) was used to assess the causal relationship between 1,400 serum metabolites and IS. The inverse variance-weighted (IVW) method was employed to estimate the causal effect between exposure and outcome. Additionally, MR-Egger regression, weighted median, simple mode, and weighted mode approaches were employed as supplementary comprehensive evaluations of the causal effects between blood metabolites and IS. Tests for pleiotropy and heterogeneity were conducted.Results: After rigorous selection, 23 known and 5 unknown metabolites were identified to be associated with IS. Among the 23 known metabolites, 13 showed significant causal effects with IS based on 2 MR methods, including 5-acetylamino-6-formylamino-3-methyluracil, 1-ribosyl-imidazoleacetate, Behenoylcarnitine (C22), N-acetyltyrosine, and N-acetylputrescine to (N (1) + N (8))-acetate,these five metabolites were positively associated with increased IS risk. Xanthurenate, Glycosyl-N-tricosanoyl-sphingadienine, Orotate, Bilirubin (E,E), Bilirubin degradation product, C17H18N2O, Bilirubin (Z,Z) to androsterone glucuronide, Bilirubin (Z,Z) to etiocholanolone glucuronide, Biliverdin, and Uridine to pseudouridine ratio were associated with decreased IS risk.Conclusion: Among 1,400 blood metabolites, this study identified 23 known metabolites that are significantly associated with IS risk, with 13 being more prominent. The integration of genomics and metabolomics provides important insights for the screening and prevention of IS.https://www.frontiersin.org/articles/10.3389/fgene.2024.1333454/fullblood metabolitesischemic strokeMendelian randomizationcausal relationshipstroke |
| spellingShingle | Menghao He Menghao He Chun Xu Renyi Yang Lijuan Liu Desheng Zhou Siyang Yan Causal relationship between human blood metabolites and risk of ischemic stroke: a Mendelian randomization study Frontiers in Genetics blood metabolites ischemic stroke Mendelian randomization causal relationship stroke |
| title | Causal relationship between human blood metabolites and risk of ischemic stroke: a Mendelian randomization study |
| title_full | Causal relationship between human blood metabolites and risk of ischemic stroke: a Mendelian randomization study |
| title_fullStr | Causal relationship between human blood metabolites and risk of ischemic stroke: a Mendelian randomization study |
| title_full_unstemmed | Causal relationship between human blood metabolites and risk of ischemic stroke: a Mendelian randomization study |
| title_short | Causal relationship between human blood metabolites and risk of ischemic stroke: a Mendelian randomization study |
| title_sort | causal relationship between human blood metabolites and risk of ischemic stroke a mendelian randomization study |
| topic | blood metabolites ischemic stroke Mendelian randomization causal relationship stroke |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2024.1333454/full |
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