Elucidating the role of hepatic enzymes in spontaneous abortion: a Mendelian randomization approach
While the hepatic enzymes Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) are crucial for liver function, their role in Spontaneous Abortion (SA) has not been thoroughly explored. Utilizing Mendelian Randomization (MR), this study aims to clarify the putative causal relationship...
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| Vydáno v: | Frontiers in genetics Ročník 15; s. 1336728 |
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02.09.2024
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| Abstract | While the hepatic enzymes Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) are crucial for liver function, their role in Spontaneous Abortion (SA) has not been thoroughly explored. Utilizing Mendelian Randomization (MR), this study aims to clarify the putative causal relationship between AST/ALT levels and SA.
Genome-wide association study (GWAS) summary data for SA (finn-b-O15_ABORT_SPONTAN), AST (ukb-d-30650_raw), and ALT (ukb-d-30620_raw) were acquired from the Integrative Epidemiology Unit OpenGWAS database. Bidirectional MR analysis was conducted using MR-Egger, Weighted Median, Simple Mode, Weighted Mode, and Inverse Variance Weighted (IVW) algorithms, and the robustness of MR results was assessed through sensitivity analyses including Heterogeneity, Horizontal Pleiotropy, and Leave-One-Out (LOO) tests. The causal role of AST and ALT's coaction in SA was explored via multivariable MR (MVMR) analysis.
The MR results via the IVW algorithm revealed a causal relation between both AST and ALT and SA (AST:
= 0.013; ALT:
= 0.017), identifying them as risk factors for SA (AST: odd ratio (OR) = 1.019; ALT: OR = 1.012). Sensitivity analysis substantiated the reliability of these results. Moreover, not notably causality was found between SA and AST/ALT (
> 0.05). Through MVMR analysis, AST and ALT demonstrated functional complementarity in the occurrence of SA, attributable to counterbalanced causalities (AST:
= 0.128; ALT:
= 0.899).
The study substantiates a causal linkage between transaminase levels and SA, enhancing our understanding of their biological interaction and the regulatory mechanisms at play. These insights could have implications for identifying novel biomarkers and therapeutic targets for SA. |
|---|---|
| AbstractList | BackgroundWhile the hepatic enzymes Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) are crucial for liver function, their role in Spontaneous Abortion (SA) has not been thoroughly explored. Utilizing Mendelian Randomization (MR), this study aims to clarify the putative causal relationship between AST/ALT levels and SA.MethodsGenome-wide association study (GWAS) summary data for SA (finn-b-O15_ABORT_SPONTAN), AST (ukb-d-30650_raw), and ALT (ukb-d-30620_raw) were acquired from the Integrative Epidemiology Unit OpenGWAS database. Bidirectional MR analysis was conducted using MR-Egger, Weighted Median, Simple Mode, Weighted Mode, and Inverse Variance Weighted (IVW) algorithms, and the robustness of MR results was assessed through sensitivity analyses including Heterogeneity, Horizontal Pleiotropy, and Leave-One-Out (LOO) tests. The causal role of AST and ALT’s coaction in SA was explored via multivariable MR (MVMR) analysis.ResultsThe MR results via the IVW algorithm revealed a causal relation between both AST and ALT and SA (AST: P = 0.013; ALT: P = 0.017), identifying them as risk factors for SA (AST: odd ratio (OR) = 1.019; ALT: OR = 1.012). Sensitivity analysis substantiated the reliability of these results. Moreover, not notably causality was found between SA and AST/ALT (P > 0.05). Through MVMR analysis, AST and ALT demonstrated functional complementarity in the occurrence of SA, attributable to counterbalanced causalities (AST: P = 0.128; ALT: P = 0.899).ConclusionThe study substantiates a causal linkage between transaminase levels and SA, enhancing our understanding of their biological interaction and the regulatory mechanisms at play. These insights could have implications for identifying novel biomarkers and therapeutic targets for SA. While the hepatic enzymes Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) are crucial for liver function, their role in Spontaneous Abortion (SA) has not been thoroughly explored. Utilizing Mendelian Randomization (MR), this study aims to clarify the putative causal relationship between AST/ALT levels and SA.BackgroundWhile the hepatic enzymes Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) are crucial for liver function, their role in Spontaneous Abortion (SA) has not been thoroughly explored. Utilizing Mendelian Randomization (MR), this study aims to clarify the putative causal relationship between AST/ALT levels and SA.Genome-wide association study (GWAS) summary data for SA (finn-b-O15_ABORT_SPONTAN), AST (ukb-d-30650_raw), and ALT (ukb-d-30620_raw) were acquired from the Integrative Epidemiology Unit OpenGWAS database. Bidirectional MR analysis was conducted using MR-Egger, Weighted Median, Simple Mode, Weighted Mode, and Inverse Variance Weighted (IVW) algorithms, and the robustness of MR results was assessed through sensitivity analyses including Heterogeneity, Horizontal Pleiotropy, and Leave-One-Out (LOO) tests. The causal role of AST and ALT's coaction in SA was explored via multivariable MR (MVMR) analysis.MethodsGenome-wide association study (GWAS) summary data for SA (finn-b-O15_ABORT_SPONTAN), AST (ukb-d-30650_raw), and ALT (ukb-d-30620_raw) were acquired from the Integrative Epidemiology Unit OpenGWAS database. Bidirectional MR analysis was conducted using MR-Egger, Weighted Median, Simple Mode, Weighted Mode, and Inverse Variance Weighted (IVW) algorithms, and the robustness of MR results was assessed through sensitivity analyses including Heterogeneity, Horizontal Pleiotropy, and Leave-One-Out (LOO) tests. The causal role of AST and ALT's coaction in SA was explored via multivariable MR (MVMR) analysis.The MR results via the IVW algorithm revealed a causal relation between both AST and ALT and SA (AST: P = 0.013; ALT: P = 0.017), identifying them as risk factors for SA (AST: odd ratio (OR) = 1.019; ALT: OR = 1.012). Sensitivity analysis substantiated the reliability of these results. Moreover, not notably causality was found between SA and AST/ALT (P > 0.05). Through MVMR analysis, AST and ALT demonstrated functional complementarity in the occurrence of SA, attributable to counterbalanced causalities (AST: P = 0.128; ALT: P = 0.899).ResultsThe MR results via the IVW algorithm revealed a causal relation between both AST and ALT and SA (AST: P = 0.013; ALT: P = 0.017), identifying them as risk factors for SA (AST: odd ratio (OR) = 1.019; ALT: OR = 1.012). Sensitivity analysis substantiated the reliability of these results. Moreover, not notably causality was found between SA and AST/ALT (P > 0.05). Through MVMR analysis, AST and ALT demonstrated functional complementarity in the occurrence of SA, attributable to counterbalanced causalities (AST: P = 0.128; ALT: P = 0.899).The study substantiates a causal linkage between transaminase levels and SA, enhancing our understanding of their biological interaction and the regulatory mechanisms at play. These insights could have implications for identifying novel biomarkers and therapeutic targets for SA.ConclusionThe study substantiates a causal linkage between transaminase levels and SA, enhancing our understanding of their biological interaction and the regulatory mechanisms at play. These insights could have implications for identifying novel biomarkers and therapeutic targets for SA. While the hepatic enzymes Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) are crucial for liver function, their role in Spontaneous Abortion (SA) has not been thoroughly explored. Utilizing Mendelian Randomization (MR), this study aims to clarify the putative causal relationship between AST/ALT levels and SA. Genome-wide association study (GWAS) summary data for SA (finn-b-O15_ABORT_SPONTAN), AST (ukb-d-30650_raw), and ALT (ukb-d-30620_raw) were acquired from the Integrative Epidemiology Unit OpenGWAS database. Bidirectional MR analysis was conducted using MR-Egger, Weighted Median, Simple Mode, Weighted Mode, and Inverse Variance Weighted (IVW) algorithms, and the robustness of MR results was assessed through sensitivity analyses including Heterogeneity, Horizontal Pleiotropy, and Leave-One-Out (LOO) tests. The causal role of AST and ALT's coaction in SA was explored via multivariable MR (MVMR) analysis. The MR results via the IVW algorithm revealed a causal relation between both AST and ALT and SA (AST: = 0.013; ALT: = 0.017), identifying them as risk factors for SA (AST: odd ratio (OR) = 1.019; ALT: OR = 1.012). Sensitivity analysis substantiated the reliability of these results. Moreover, not notably causality was found between SA and AST/ALT ( > 0.05). Through MVMR analysis, AST and ALT demonstrated functional complementarity in the occurrence of SA, attributable to counterbalanced causalities (AST: = 0.128; ALT: = 0.899). The study substantiates a causal linkage between transaminase levels and SA, enhancing our understanding of their biological interaction and the regulatory mechanisms at play. These insights could have implications for identifying novel biomarkers and therapeutic targets for SA. |
| Author | Li, Zhenghong Liu, Xingfang Zhu, Yingping Wen, Chengping |
| AuthorAffiliation | 1 The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) , Hangzhou , China 2 Research Department , Swiss University of Traditional Chinese Medicine , Bad Zurzach , Switzerland 4 Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province , Hangzhou , China 3 College of Basic Medical Science , Zhejiang Chinese Medical University , Hangzhou , China |
| AuthorAffiliation_xml | – name: 4 Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province , Hangzhou , China – name: 3 College of Basic Medical Science , Zhejiang Chinese Medical University , Hangzhou , China – name: 2 Research Department , Swiss University of Traditional Chinese Medicine , Bad Zurzach , Switzerland – name: 1 The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) , Hangzhou , China |
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| Keywords | alanine aminotransferase (ALT) spontaneous abortion (SA) Mendelian randomization (MR) hepatic enzymes aspartate aminotransferase (AST) |
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| SubjectTerms | alanine aminotransferase (ALT) aspartate aminotransferase (AST) Genetics hepatic enzymes Mendelian randomization (MR) spontaneous abortion (SA) |
| Title | Elucidating the role of hepatic enzymes in spontaneous abortion: a Mendelian randomization approach |
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