Evidence map›Paper›PMID 39015781›Full record

ArticleFrontiers in medicine2024

Causality of metabolites and metabolic pathways on cholestatic liver diseases: a Mendelian randomization study.

Zhengxiao Wei, Yingfen Liu, Qingqing Xiong, Xue Mei, Jinghong Li, Zhangjun Wu

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Article in Frontiers in medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Zhengxiao Wei *Department of Clinical Laboratory, Public Health Clinical Center of Chengdu, Chengdu, China.
Yingfen Liu *Department of Clinical Laboratory, Public Health Clinical Center of Chengdu, Chengdu, China.
Qingqing XiongDepartment of Science and Education Division, Public Health Clinical Center of Chengdu, Chengdu, China.
Xue MeiDepartment of Infectious Diseases, Public Health Clinical Center of Chengdu, Chengdu, China.
Jinghong LiDepartment of Infectious Diseases, Public Health Clinical Center of Chengdu, Chengdu, China.
Zhangjun WuDepartment of Clinical Laboratory, Public Health Clinical Center of Chengdu, Chengdu, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background and Aims: Blood metabolite abnormalities have revealed an association with cholestatic liver diseases (CLDs), while the underlying metabolic mechanisms have remained sluggish yet. Accordingly, the present evaluation aims to investigate the causal relationship between blood metabolites and the risk of two major CLDs, including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Methods: Univariable and multivariable Mendelian randomization (MR) approaches were employed to uncover potential causal associations between blood metabolites and 2 CLDs, including PBS and PSC, through extracting instrumental variables (IVs) for metabolites from genome-wide association studies (GWAS) conducted on European individuals. The GWAS summary data of PBC or PSC were sourced from two distinct datasets. The initial analysis employed inverse variance weighted (IVW) and an array of sensitivity analyses, followed by replication and meta-analysis utilizing FinnGen consortium data. Finally, a multivariable MR analysis was carried out to ascertain the independent effects of each metabolite. Furthermore, the web-based tool MetaboAnalyst 5.0 was used to perform metabolic pathway examination. Results: A genetic causality between 15 metabolites and CLDs was recognized after preliminary analysis and false discovery rate (FDR) correction. Subsequently, 9 metabolites consistently represented an association through replication and meta-analysis. Additionally, the independent causal effects of 7 metabolites were corroborated by multivariable MR analysis. Specifically, the metabolites isovalerylcarnitine (odds ratio [OR] = 3.146, 95% confidence intervals [CI]: 1.471-6.726, Conclusion: The findings of the present study have unveiled robust causal relationships between 7 metabolites and 2 CLDs, thereby providing novel insights into the metabolic mechanisms and therapeutic strategies for these disorders.

Indexed as

blood metaboliteschloestatic liver diseasesMendelian randomizationmetabolic pathwayprimary biliary cholangitisprimary sclerosing cholangitis

Identifiers

PMID39015781
PMCPMC11250271

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