Causal Effects Between Genetically Determined Human Serum Metabolite Levels on the Risk of Idiopathic Pulmonary Fibrosis: A Mendelian Randomization Study

ABSTRACT Background The incidence of idiopathic pulmonary fibrosis (IPF) is increasing every year; however, the potential biological mechanisms have not been completely clarified. The objective of this study is to reveal the etiologic effects of circulating metabolites on IPF. Methods This research...

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Main Authors: Yu Shi, Shuang Chen, Zhaokai Zhou, Mengke Huang, Yue Li, Xiaogang Jing
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:The Clinical Respiratory Journal
Subjects:
Online Access:https://doi.org/10.1111/crj.70087
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author Yu Shi
Shuang Chen
Zhaokai Zhou
Mengke Huang
Yue Li
Xiaogang Jing
author_facet Yu Shi
Shuang Chen
Zhaokai Zhou
Mengke Huang
Yue Li
Xiaogang Jing
author_sort Yu Shi
collection DOAJ
description ABSTRACT Background The incidence of idiopathic pulmonary fibrosis (IPF) is increasing every year; however, the potential biological mechanisms have not been completely clarified. The objective of this study is to reveal the etiologic effects of circulating metabolites on IPF. Methods This research evaluated the causal relationship between serum metabolites and IPF utilizing two‐sample Mendelian randomization (MR) analysis. IVW served as the main method of analysis; concurrently, MR‐Egger, weighted median, and MR‐PRESSO acted as supplementary analyses. Sensitivity analyses were performed with Cochran's Q test, MR‐Egger's intercept test, and leave‐one‐out method of analysis. All statistical analyses were accomplished in R software. Results Our results showed that 23 metabolites have a causal connection with IPF. Following sensitivity analysis, 2 robust and 12 potential causal association pairs were identified among the known metabolites. These 14 causal pairs concerned six metabolites. Conclusion This study presents a novel perspective on potential mechanisms involved in IPF with important significance for screening, prevention, and treatment.
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institution Kabale University
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publishDate 2025-06-01
publisher Wiley
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series The Clinical Respiratory Journal
spelling doaj-art-e14eb64c7490427088f6c36070dffe592025-08-20T03:32:15ZengWileyThe Clinical Respiratory Journal1752-69811752-699X2025-06-01196n/an/a10.1111/crj.70087Causal Effects Between Genetically Determined Human Serum Metabolite Levels on the Risk of Idiopathic Pulmonary Fibrosis: A Mendelian Randomization StudyYu Shi0Shuang Chen1Zhaokai Zhou2Mengke Huang3Yue Li4Xiaogang Jing5Department of Respiration The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan ChinaCenter of Reproductive Medicine The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan ChinaDepartment of Urology The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan ChinaDepartment of Respiration The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan ChinaDepartment of Respiration The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan ChinaDepartment of Respiration The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan ChinaABSTRACT Background The incidence of idiopathic pulmonary fibrosis (IPF) is increasing every year; however, the potential biological mechanisms have not been completely clarified. The objective of this study is to reveal the etiologic effects of circulating metabolites on IPF. Methods This research evaluated the causal relationship between serum metabolites and IPF utilizing two‐sample Mendelian randomization (MR) analysis. IVW served as the main method of analysis; concurrently, MR‐Egger, weighted median, and MR‐PRESSO acted as supplementary analyses. Sensitivity analyses were performed with Cochran's Q test, MR‐Egger's intercept test, and leave‐one‐out method of analysis. All statistical analyses were accomplished in R software. Results Our results showed that 23 metabolites have a causal connection with IPF. Following sensitivity analysis, 2 robust and 12 potential causal association pairs were identified among the known metabolites. These 14 causal pairs concerned six metabolites. Conclusion This study presents a novel perspective on potential mechanisms involved in IPF with important significance for screening, prevention, and treatment.https://doi.org/10.1111/crj.70087causalityidiopathic pulmonary fibrosisMendelian randomizationserum metabolites
spellingShingle Yu Shi
Shuang Chen
Zhaokai Zhou
Mengke Huang
Yue Li
Xiaogang Jing
Causal Effects Between Genetically Determined Human Serum Metabolite Levels on the Risk of Idiopathic Pulmonary Fibrosis: A Mendelian Randomization Study
The Clinical Respiratory Journal
causality
idiopathic pulmonary fibrosis
Mendelian randomization
serum metabolites
title Causal Effects Between Genetically Determined Human Serum Metabolite Levels on the Risk of Idiopathic Pulmonary Fibrosis: A Mendelian Randomization Study
title_full Causal Effects Between Genetically Determined Human Serum Metabolite Levels on the Risk of Idiopathic Pulmonary Fibrosis: A Mendelian Randomization Study
title_fullStr Causal Effects Between Genetically Determined Human Serum Metabolite Levels on the Risk of Idiopathic Pulmonary Fibrosis: A Mendelian Randomization Study
title_full_unstemmed Causal Effects Between Genetically Determined Human Serum Metabolite Levels on the Risk of Idiopathic Pulmonary Fibrosis: A Mendelian Randomization Study
title_short Causal Effects Between Genetically Determined Human Serum Metabolite Levels on the Risk of Idiopathic Pulmonary Fibrosis: A Mendelian Randomization Study
title_sort causal effects between genetically determined human serum metabolite levels on the risk of idiopathic pulmonary fibrosis a mendelian randomization study
topic causality
idiopathic pulmonary fibrosis
Mendelian randomization
serum metabolites
url https://doi.org/10.1111/crj.70087
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