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Pediatric Rheumatology
Published in: Pediatric Rheumatology 1/2024

Open Access 01-12-2024 | Juvenile Rheumatoid Arthritis | Research article

Causal relationship between serum metabolites and juvenile idiopathic arthritis: a mendelian randomization study

Authors: Han Zhang, Xiao Ma, Wanlu Liu, Ze Wang, Zian Zhang, GuanHong Chen, Yingze Zhang, Tianrui Wang, Tengbo Yu, Yongtao Zhang

Published in: Pediatric Rheumatology | Issue 1/2024

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Abstract

Background

Juvenile Idiopathic Arthritis (JIA) is a condition that occurs when individuals under the age of 16 develop arthritis that lasts for more than six weeks, and the cause is unknown. The development of JIA may be linked to serum metabolites. Nevertheless, the association between JIA pathogenesis and serum metabolites is unclear, and there are discrepancies in the findings across studies.

Methods

In this research, the association between JIA in humans and 486 serum metabolites was assessed using genetic variation data and genome-wide association study. The identification of causal relationships was accomplished through the application of univariate Mendelian randomization (MR) analysis. Various statistical methods, including inverse variance weighted and MR-Egger, were applied to achieve this objective. To ensure that the findings from the MR analysis were trustworthy, a number of assessments were carried out. To ensure the accuracy of the obtained results, a range of techniques were utilised including the Cochran Q test, examination of the MR-Egger intercept, implementation of the leave-one-out strategy, and regression analysis of linkage disequilibrium scores. In order to identify the specific metabolic pathways associated with JIA, our primary objective was to perform pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes.

Results

Two-sample summary data MR analyses and sensitivity analyses showed that five metabolites were significantly causally associated with JIA, including two risk factors—kynurenine (odds ratio [OR]: 16.39, 95% confidence interval [CI]: 2.07-129.63, p = 5.11 × 10− 6) and linolenate (OR: 16.48, 95% CI: 1.32-206.22, p = 0.030)—and three protective factors—3-dehydrocarnitine (OR: 0.32, 95% CI: 0.14–0.72, p = 0.007), levulinate (4-oxovalerate) (OR: 0.40, 95% CI: 0.20–0.80, p = 0.010), and X-14,208 (phenylalanylserine) (OR: 0.68, 95% CI: 0.51–0.92, p = 0.010). Furthermore, seven metabolic pathways, including α-linolenic acid metabolism and pantothenate and CoA biosynthesis, are potentially associated with the onset and progression of JIA.

Conclusion

Five serum metabolites, including kynurenine and 3-dehydrocarnitine, may be causally associated with JIA. These results provide a theoretical framework for developing effective JIA prevention and screening strategies.
Appendix
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Metadata
Title
Causal relationship between serum metabolites and juvenile idiopathic arthritis: a mendelian randomization study
Authors
Han Zhang
Xiao Ma
Wanlu Liu
Ze Wang
Zian Zhang
GuanHong Chen
Yingze Zhang
Tianrui Wang
Tengbo Yu
Yongtao Zhang
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Pediatric Rheumatology / Issue 1/2024
Electronic ISSN: 1546-0096
DOI
https://doi.org/10.1186/s12969-024-00986-0

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