Evaluating the causal relationship between human blood metabolites and gastroesophageal reflux disease
Gastroesophageal reflux disease (GERD) affects approximately 13% of the global population. However, the pathogenesis of GERD has not been fully elucidated. The development of metabolomics as a branch of systems biology in recent years has opened up new avenues for the investigation of disease proces...
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Published in | World journal of gastrointestinal oncology Vol. 15; no. 12; pp. 2169 - 2184 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
China
Baishideng Publishing Group Inc
15.12.2023
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Subjects | |
Online Access | Get full text |
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Summary: | Gastroesophageal reflux disease (GERD) affects approximately 13% of the global population. However, the pathogenesis of GERD has not been fully elucidated. The development of metabolomics as a branch of systems biology in recent years has opened up new avenues for the investigation of disease processes. As a powerful statistical tool, Mendelian randomization (MR) is widely used to explore the causal relationship between exposure and outcome.
To analyze of the relationship between 486 blood metabolites and GERD.
Two-sample MR analysis was used to assess the causal relationship between blood metabolites and GERD. A genome-wide association study (GWAS) of 486 metabolites was the exposure, and two different GWAS datasets of GERD were used as endpoints for the base analysis and replication and meta-analysis. Bonferroni correction is used to determine causal correlation features (
< 1.03 × 10
). The results were subjected to sensitivity analysis to assess heterogeneity and pleiotropy. Using the MR Steiger filtration method to detect whether there is a reverse causal relationship between metabolites and GERD. In addition, metabolic pathway analysis was conducted using the online database based MetaboAnalyst 5.0 software.
In MR analysis, four blood metabolites are negatively correlated with GERD: Levulinate (4-oxovalerate), stearate (18:0), adrenate (22:4n6) and p-acetamidophenylglucuronide. However, we also found a positive correlation between four blood metabolites and GERD: Kynurenine, 1-linoleoylglycerophosphoethanolamine, butyrylcarnitine and guanosine. And bonferroni correction showed that butyrylcarnitine (odd ratio 1.10, 95% confidence interval: 1.05-1.16,
= 7.71 × 10
) was the most reliable causal metabolite. In addition, one significant pathways, the "glycerophospholipid metabolism" pathway, can be involved in the pathogenesis of GERD.
Our study found through the integration of genomics and metabolomics that butyrylcarnitine may be a potential biomarker for GERD, which will help further elucidate the pathogenesis of GERD and better guide its treatment. At the same time, this also contributes to early screening and prevention of GERD. However, the results of this study require further confirmation from both basic and clinical real-world studies. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author contributions: Hu JY and Lv M designed the research; Hu JY, Zhang KL, Qiao XY collected and analyzed the data; Hu JY, Lv M and Zhang KL drafted the manuscript; Qiao XY, Wang YX and Wang FY revised the manuscript; Wang FY for the entire text; all authors contributed to the article and approved the submitted version. Supported by National Natural Science Foundation of China, No. 82174363. Corresponding author: Feng-Yun Wang, PhD, Chief Doctor, Professor, Institute of Digestive Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, No. 1 Courtyard, Xiyuan Playground, Haidian District, Beijing 100091, China. wfy811@163.com |
ISSN: | 1948-5204 1948-5204 |
DOI: | 10.4251/wjgo.v15.i12.2169 |