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Using a Two-Sample Mendelian Randomization Method in Assessing the Causal Relationships Between Human Blood Metabolites and Heart Failure

Background: Heart failure (HF) is the main cause of morbidity and mortality worldwide, and metabolic dysfunction is an important factor related to HF pathogenesis and development. However, the causal effect of blood metabolites on HF remains unclear. Objectives: Our chief aim is to investigate the c...

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Autores principales: Wang, Zixian, Chen, Shiyu, Zhu, Qian, Wu, Yonglin, Xu, Guifeng, Guo, Gongjie, Lai, Weihua, Chen, Jiyan, Zhong, Shilong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476837/
https://www.ncbi.nlm.nih.gov/pubmed/34595216
http://dx.doi.org/10.3389/fcvm.2021.695480
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author Wang, Zixian
Chen, Shiyu
Zhu, Qian
Wu, Yonglin
Xu, Guifeng
Guo, Gongjie
Lai, Weihua
Chen, Jiyan
Zhong, Shilong
author_facet Wang, Zixian
Chen, Shiyu
Zhu, Qian
Wu, Yonglin
Xu, Guifeng
Guo, Gongjie
Lai, Weihua
Chen, Jiyan
Zhong, Shilong
author_sort Wang, Zixian
collection PubMed
description Background: Heart failure (HF) is the main cause of morbidity and mortality worldwide, and metabolic dysfunction is an important factor related to HF pathogenesis and development. However, the causal effect of blood metabolites on HF remains unclear. Objectives: Our chief aim is to investigate the causal relationships between human blood metabolites and HF risk. Methods: We used an unbiased two-sample Mendelian randomization (MR) approach to assess the causal relationships between 486 human blood metabolites and HF risk. Exposure information was obtained from Sample 1, which is the largest metabolome-based genome-wide association study (mGWAS) data containing 7,824 Europeans. Outcome information was obtained from Sample 2, which is based on the results of a large-scale GWAS meta-analysis of HF and contains 47,309 cases and 930,014 controls of Europeans. The inverse variance weighted (IVW) model was used as the primary two-sample MR analysis method and followed the sensitivity analyses, including heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis. Results: We observed that 11 known metabolites were potentially related to the risk of HF after using the IVW method (P < 0.05). After adding another four MR models and performing sensitivity analyses, we found a 1-SD increase in the xenobiotics 4-vinylphenol sulfate was associated with ~22% higher risk of HF (OR [95%CI], 1.22 [1.07–1.38]). Conclusions: We revealed that the 4-vinylphenol sulfate may nominally increase the risk of HF by 22% after using a two-sample MR approach. Our findings may provide novel insights into the pathogenesis underlying HF and novel strategies for HF prevention.
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spelling pubmed-84768372021-09-29 Using a Two-Sample Mendelian Randomization Method in Assessing the Causal Relationships Between Human Blood Metabolites and Heart Failure Wang, Zixian Chen, Shiyu Zhu, Qian Wu, Yonglin Xu, Guifeng Guo, Gongjie Lai, Weihua Chen, Jiyan Zhong, Shilong Front Cardiovasc Med Cardiovascular Medicine Background: Heart failure (HF) is the main cause of morbidity and mortality worldwide, and metabolic dysfunction is an important factor related to HF pathogenesis and development. However, the causal effect of blood metabolites on HF remains unclear. Objectives: Our chief aim is to investigate the causal relationships between human blood metabolites and HF risk. Methods: We used an unbiased two-sample Mendelian randomization (MR) approach to assess the causal relationships between 486 human blood metabolites and HF risk. Exposure information was obtained from Sample 1, which is the largest metabolome-based genome-wide association study (mGWAS) data containing 7,824 Europeans. Outcome information was obtained from Sample 2, which is based on the results of a large-scale GWAS meta-analysis of HF and contains 47,309 cases and 930,014 controls of Europeans. The inverse variance weighted (IVW) model was used as the primary two-sample MR analysis method and followed the sensitivity analyses, including heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis. Results: We observed that 11 known metabolites were potentially related to the risk of HF after using the IVW method (P < 0.05). After adding another four MR models and performing sensitivity analyses, we found a 1-SD increase in the xenobiotics 4-vinylphenol sulfate was associated with ~22% higher risk of HF (OR [95%CI], 1.22 [1.07–1.38]). Conclusions: We revealed that the 4-vinylphenol sulfate may nominally increase the risk of HF by 22% after using a two-sample MR approach. Our findings may provide novel insights into the pathogenesis underlying HF and novel strategies for HF prevention. Frontiers Media S.A. 2021-09-14 /pmc/articles/PMC8476837/ /pubmed/34595216 http://dx.doi.org/10.3389/fcvm.2021.695480 Text en Copyright © 2021 Wang, Chen, Zhu, Wu, Xu, Guo, Lai, Chen and Zhong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Wang, Zixian
Chen, Shiyu
Zhu, Qian
Wu, Yonglin
Xu, Guifeng
Guo, Gongjie
Lai, Weihua
Chen, Jiyan
Zhong, Shilong
Using a Two-Sample Mendelian Randomization Method in Assessing the Causal Relationships Between Human Blood Metabolites and Heart Failure
title Using a Two-Sample Mendelian Randomization Method in Assessing the Causal Relationships Between Human Blood Metabolites and Heart Failure
title_full Using a Two-Sample Mendelian Randomization Method in Assessing the Causal Relationships Between Human Blood Metabolites and Heart Failure
title_fullStr Using a Two-Sample Mendelian Randomization Method in Assessing the Causal Relationships Between Human Blood Metabolites and Heart Failure
title_full_unstemmed Using a Two-Sample Mendelian Randomization Method in Assessing the Causal Relationships Between Human Blood Metabolites and Heart Failure
title_short Using a Two-Sample Mendelian Randomization Method in Assessing the Causal Relationships Between Human Blood Metabolites and Heart Failure
title_sort using a two-sample mendelian randomization method in assessing the causal relationships between human blood metabolites and heart failure
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476837/
https://www.ncbi.nlm.nih.gov/pubmed/34595216
http://dx.doi.org/10.3389/fcvm.2021.695480
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