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Abstract：
BACKGROUND: Existing studies have presented limited and disparate findings on the nexus between immune cells, plasma metabolites, and metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of this study was to investigate the causal relationship between immune cells and MASLD. Additionally, we aimed to identify and quantify the potential mediating role of metabolites.
METHODS: A Mendelian randomization (MR) analysis was conducted using two samples of pooled data from genome-wide association studies on MASLD that included 2568 patients and 409,613 control individuals. Additionally, a mediated MR study was employed to quantify the metabolite-mediated immune cell effects on MASLD.
RESULTS: In this study, eight immunophenotypes were linked to the risk of MASLD, and thirty-five metabolites/metabolite ratios were linked to the occurrence of MASLD. Furthermore, a total of six combinations of immunophenotypic and metabolic factors demonstrated effects on the occurrence of MASLD, although the mediating effects of metabolites were not significant.
CONCLUSIONS: Our study demonstrated that certain immunophenotypes and metabolite/metabolite ratios have independent causal relationships with MASLD. Furthermore, we identified specific metabolites/metabolite ratios that are associated with an increased risk of MASLD. However, their mediating role in the causal association between immunophenotypes and MASLD was not significant. It is important to consider immune and metabolic disorders among patients with MASLD in clinical practice.
METHODS: A Mendelian randomization (MR) analysis was conducted using two samples of pooled data from genome-wide association studies on MASLD that included 2568 patients and 409,613 control individuals. Additionally, a mediated MR study was employed to quantify the metabolite-mediated immune cell effects on MASLD.
RESULTS: In this study, eight immunophenotypes were linked to the risk of MASLD, and thirty-five metabolites/metabolite ratios were linked to the occurrence of MASLD. Furthermore, a total of six combinations of immunophenotypic and metabolic factors demonstrated effects on the occurrence of MASLD, although the mediating effects of metabolites were not significant.
CONCLUSIONS: Our study demonstrated that certain immunophenotypes and metabolite/metabolite ratios have independent causal relationships with MASLD. Furthermore, we identified specific metabolites/metabolite ratios that are associated with an increased risk of MASLD. However, their mediating role in the causal association between immunophenotypes and MASLD was not significant. It is important to consider immune and metabolic disorders among patients with MASLD in clinical practice.
摘要：
背景：现有研究对免疫细胞之间的联系提出了有限和不同的发现，血浆代谢物，和代谢功能障碍相关的脂肪变性肝病（MASLD）。本研究旨在探讨免疫细胞与MASLD之间的因果关系。此外,我们旨在鉴定和量化代谢物的潜在介导作用.
方法：孟德尔随机化（MR）分析使用来自MASLD全基因组关联研究的两个数据样本进行，包括2568名患者和409,613名对照个体。此外,一项介导的MR研究用于定量代谢物介导的免疫细胞对MASLD的影响.
结果：在这项研究中，八种免疫表型与MASLD的风险有关，35种代谢物/代谢物比率与MASLD的发生有关。此外，共有6种免疫表型和代谢因子组合显示了对MASLD发生的影响，虽然代谢产物的介导作用不显著。
结论：我们的研究表明，某些免疫表型和代谢物/代谢物比率与MASLD具有独立的因果关系。此外，我们确定了与MASLD风险增加相关的特定代谢物/代谢物比率.然而,它们在免疫表型和MASLD之间的因果关系中的中介作用不显著.在临床实践中，重要的是要考虑MASLD患者的免疫和代谢紊乱。
方法：孟德尔随机化（MR）分析使用来自MASLD全基因组关联研究的两个数据样本进行，包括2568名患者和409,613名对照个体。此外,一项介导的MR研究用于定量代谢物介导的免疫细胞对MASLD的影响.
结果：在这项研究中，八种免疫表型与MASLD的风险有关，35种代谢物/代谢物比率与MASLD的发生有关。此外，共有6种免疫表型和代谢因子组合显示了对MASLD发生的影响，虽然代谢产物的介导作用不显著。
结论：我们的研究表明，某些免疫表型和代谢物/代谢物比率与MASLD具有独立的因果关系。此外，我们确定了与MASLD风险增加相关的特定代谢物/代谢物比率.然而,它们在免疫表型和MASLD之间的因果关系中的中介作用不显著.在临床实践中，重要的是要考虑MASLD患者的免疫和代谢紊乱。
