Bidirectional two-sample Mendelian randomization reveals causal link between genetic blood metabolites and tuberculosis.

IF 3.5 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Zhenyu Shi, Chenyi Zhao, Xiaowen Yu, Dingding Zhao, Yongqiang Li
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Abstract

Tuberculosis (TB), caused by infectious agent Mycobacterium tuberculosis (Mtb) seriously poses a great threat to health. An array of metabolites generated by metabolic pathways are essential for Mtb pathophysiology. However, a specific causal relationship between TB and human metabolites remains indistinct. This study aimed to investigate the relationship between 1400 metabolites and TB by Mendelian randomization (MR) analysis. In this study, a total of 1400 metabolites were utilized as exposure factors, while TB-related data served as the outcomes. And TwoSampleMR package and R software were adopted to perform this MR analysis. Various regression fitting methods were employed to conduct MR analysis, including inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode. In addition, potential biases arising from linkage disequilibrium and weak instrumental variables were considered. Metabolites that failed to meet the criteria in both the heterogeneity and pleiotropy tests were considered to have no substantial causal influence on the results, ensuring the robustness and reliability of our analysis. IVW analysis showed that six human metabolites exhibited a significant causal influence (P < 0.05) on TB. Among them, dodecanedioate, myristoleate (14:1n5), and 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE(p-16:0/20:4) demonstrated a strong causally positive effect on TB, indicating that with the increase of these metabolites, TB progressed robustly. Glycerol 3-phosphate, sphingomyelin (d18:1/20:2, d18:2/20:1, and d16:1/22:2), and 2-methylserine were significantly negatively associated with TB, an increase in these metabolites inhibited TB progression. This is the first time to reveal the causal effects of human metabolites on TB through MR, and the metabolites may be potential biomarkers candidate for TB diagnosis, and monitoring these metabolites might have great clinic significance for TB diagnosis and treatment in the future.

双向双样本孟德尔随机化揭示了遗传血液代谢物与结核病之间的因果关系。
由传染性病原体结核分枝杆菌(Mycobacterium Tuberculosis, Mtb)引起的结核病严重威胁着人类的健康。代谢途径产生的一系列代谢物对结核分枝杆菌的病理生理至关重要。然而,结核病与人类代谢物之间的具体因果关系仍不清楚。本研究旨在通过孟德尔随机化(MR)分析,探讨1400种代谢物与结核病的关系。在本研究中,共有1400种代谢物作为暴露因子,而结核病相关数据作为结果。采用TwoSampleMR软件包和R软件进行MR分析。采用各种回归拟合方法进行MR分析,包括逆方差加权(IVW)、MR- egger、加权中位数、简单模式和加权模式。此外,还考虑了由联动不平衡和弱工具变量引起的潜在偏差。在异质性和多效性试验中未能满足标准的代谢物被认为对结果没有实质性的因果影响,从而确保了我们分析的稳健性和可靠性。IVW分析显示,六种人体代谢物表现出显著的因果影响(P
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来源期刊
AMB Express
AMB Express BIOTECHNOLOGY & APPLIED MICROBIOLOGY-
CiteScore
7.20
自引率
2.70%
发文量
141
审稿时长
13 weeks
期刊介绍: AMB Express is a high quality journal that brings together research in the area of Applied and Industrial Microbiology with a particular interest in ''White Biotechnology'' and ''Red Biotechnology''. The emphasis is on processes employing microorganisms, eukaryotic cell cultures or enzymes for the biosynthesis, transformation and degradation of compounds. This includes fine and bulk chemicals, polymeric compounds and enzymes or other proteins. Downstream processes are also considered. Integrated processes combining biochemical and chemical processes are also published.
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