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ORIGINAL RESEARCH article

Front. Cardiovasc. Med.
Sec. Hypertension
Volume 11 - 2024 | doi: 10.3389/fcvm.2024.1304986
This article is part of the Research Topic Emerging Molecules in Pulmonary Hypertension: Diagnosis, Risk Prediction, Treatment and Prognosis View all articles

Investigating the causal relationship between human blood metabolites and pulmonary hypertension：a two-sample Mendelian randomization study

Provisionally accepted
Xingdu Zeng Xingdu Zeng Bin Zhong Bin Zhong *
  • Department of Respiratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi Province, China

The final, formatted version of the article will be published soon.

    Background: Several recent investigations have posited that distinct metabolites in the bloodstream may be correlated with the pathogenesis of Pulmonary Hypertension (PH). Nonetheless, the interrelationship between the pathogenesis of PH and metabolite fluctuations remains incompletely elucidated, and findings may differ across studies.In the extant research, data from 486 metabolite-and PH-related genetic variants in human subjects were procured based on Genome-Wide Association Studies (GWAS) and Finnish databases.Univariate Mendelian Randomization analyses were deployed to evaluate the causal relationships between them. The utilization of the randomized Inverse Variance weighted(IVW) method served as the primary analytic framework in this Mendelian Randomization (MR) study. Additionally, four alternative computational strategies, encompassing MR-Egger, were employed as auxiliary methods.A myriad of tests, including Cochran's Q Test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and linkage disequilibrium score were incorporated to assess the robustness of the study outcomes. Metabolite pathway analysis was also executed to identify potential metabolic pathways.Results: After a series of validations and corrected for False discovery rate (FDR), we found a significant association between 1,5-anhydroglucitol (OR=2.00, 95% CI: 1.39-2.89, P=0.0002) and PH, and a significant association between pyridoxalate (OR=0.59, 95% CI: 0.43-0.81, P=0.0009) and 1-a achidonoylglycerophosphocholine (OR=1.78, 95% CI: 1.22-2.58, P=0.0026) had a suggested association with PH. In addition, the vitamin B6 metabolic pathway was also determined to be associated with PH.Conclusively, we isolated 1,5-anhydroglucitol, 1-arachidonoylglycerophosphocholine, and pyridoxate as causally implicated in PH, thereby proffering substantial theoretical substantiation for the formulation of future PH prevention and screening paradigms.

    Keywords: Serological Metabolites, Mendelian randomization, pulmonary hypertension, Instrumental variables, causal inference

    Received: 30 Sep 2023; Accepted: 27 Sep 2024.

    Copyright: © 2024 Zeng and Zhong. 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) or licensor 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.

    * Correspondence: Bin Zhong, Department of Respiratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi Province, China

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