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. 2024 May 21;14(1):11551.
doi: 10.1038/s41598-024-58160-1.

Mendelian randomization analysis reveals causal associations of serum metabolites with sepsis and 28-day mortality

Guoqing Jing #  1 , Jing Zuo #  1 , Zhi Liu  2 , Huifan Liu  1 , Miao Cheng  3 , Min Yuan  4 , Hailong Gong  1 , Xiaojing Wu  5 , Xuemin Song  6
Affiliations

Mendelian randomization analysis reveals causal associations of serum metabolites with sepsis and 28-day mortality

Guoqing Jing et al. Sci Rep. .

Abstract

Metabolic disorder has been found to be an important factor in the pathogenesis and progression of sepsis. However, the causation of such an association between serum metabolites and sepsis has not been established. We conducted a two-sample Mendelian randomization (MR) study. A genome-wide association study of 486 human serum metabolites was used as the exposure, whereas sepsis and sepsis mortality within 28 days were set as the outcomes. In MR analysis, 6 serum metabolites were identified to be associated with an increased risk of sepsis, and 6 serum metabolites were found to be related to a reduced risk of sepsis. Furthermore, there were 9 metabolites positively associated with sepsis-related mortality, and 8 metabolites were negatively correlated with sepsis mortality. In addition, "glycolysis/gluconeogenesis" (p = 0.001), and "pyruvate metabolism" (p = 0.042) two metabolic pathways were associated with the incidence of sepsis. This MR study suggested that serum metabolites played significant roles in the pathogenesis of sepsis, which may provide helpful biomarkers for early disease diagnosis, therapeutic interventions, and prognostic assessments for sepsis.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Overview of this Mendelian randomization (MR) analysis. Assumption 1: The genetic instruments are directly associated with the exposure. Assumption 2: Genetic instruments have no impact on the outcome and are independent of known and unknown confounders. Assumption 3: Genetic instruments are unrelated to the outcome and affect the outcome entirely through exposure.
Figure 2
Figure 2
Causal association heatmap of serum metabolites with sepsis and 28-day mortality in sepsis by IVW analysis. Rows in the figure represent different serum metabolites, while columns depict two outcomes: sepsis and 28-day mortality in sepsis. Different metabolites are presented in distinct colors, with pink and blue indicating positive and negative factors, respectively. Deeper colors on the heatmap signify higher significance.
Figure 3
Figure 3
Forest plot for the causal effect of metabolites on the risk of sepsis by IVW, Weighted median, MR-PRESSO, and MR-Egger methods. Nsnp, number of SNP; OR, odds ratio; CI, confidence interval.
Figure 4
Figure 4
Forest plot for the causal effect of metabolites on the risk of sepsis mortality within 28 days by IVW, Weighted median, MR-PRESSO, and MR-Egger methods. Nsnp, number of SNP; OR, odds ratio; CI, confidence interval.
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