通过孟德尔随机化研究评估代谢生物标志物与川崎病之间的因果关系

Assessing the Causal Relationship between Metabolic Biomarkers and Kawasaki Disease by Mendelian Randomization Studies

摘要: 目的：本研究旨在通过双样本孟德尔随机化(MR)分析，探讨血液代谢物与川崎病之间的因果关系，为识别川崎病的潜在生物标志物提供可能的科学依据。方法：采用双样本孟德尔随机化分析方法，评估血液代谢物与川崎病的关联性。为估算因果关系，我们运用了逆方差加权(IVW)方法。此外，进行敏感性分析时，采用了MR-Egger、加权中位数和MR-PRESSO等方法。同时，利用MR-Egger回归和Cochran’s Q统计量评估潜在的异质性和多效性。结果：研究揭示三种代谢物与川崎病之间可能存在关联。其中，X-17654 (IVW:OR = 2.078, 95%CI: 1.157~3.732, P < 0.05)与川崎病风险呈正相关；而1-(1-烯基-棕榈酰)-2-棕榈油酰-GPC (IVW:OR = 0.476, 95%CI: 0.260~0.874, P < 0.05)和琥珀酸与脯氨酸比值(IVW:OR = 0.184, 95%CI: 0.064~0.530, P < 0.05)两种代谢物与川崎病呈负相关。敏感性分析未发现显著的异质性和多效性。结论：本MR研究凸显了代谢物在川崎病发病中的因果作用，并鉴定出具有潜在风险或保护效应的代谢物。这些发现为川崎病的发病机制研究、早期预防及治疗策略的制定提供了可能。文章也存在一些局限和不足之处，由于当前研究所依赖的数据库资源和样本量有限，所得结果可能存在一定的偏倚性。

Abstract: Objective: This study aimed to investigate the causal relationship between blood metabolites and Kawasaki disease through a two-sample Mendelian randomization (MR) analysis, thereby providing a potential scientific basis for identifying potential biomarkers of Kawasaki disease. Methods: A two-sample Mendelian randomization analysis was employed to assess the association between blood metabolites and Kawasaki disease. The inverse-variance weighted (IVW) method was used to estimate causal effects. Sensitivity analyses were conducted using MR-Egger, weighted median, and MR-PRESSO methods. Additionally, MR-Egger regression and Cochran’s Q statistic were applied to evaluate potential heterogeneity and pleiotropy. Results: The study reveals that three metabolites may be associated with Kawasaki disease. Among them, metabolite X-17654 showed a positive correlation with Kawasaki disease risk (IVW:OR = 2.078, 95% CI: 1.157~3.732, P < 0.05). In contrast, two metabolites 1-(1-enyl-palmitoyl)-2-palmitoleoyl-GPC (IVW:OR = 0.476, 95%CI: 0.260~0.874, P < 0.05) and the succinate-to-proline ratio (IVW:OR = 0.184, 95%CI: 0.064~0.530, P < 0.05) were negatively correlated with Kawasaki disease. Sensitivity analyses revealed no significant heterogeneity or pleiotropy. Conclusion: This MR study highlights the causal role of metabolites in the pathogenesis of Kawasaki disease and identifies specific metabolites with potential risk or protective effects. These findings may provide insights into the pathogenesis of Kawasaki disease, as well as its early prevention and treatment strategies. However, the study also has certain limitations and shortcomings, as the current research is constrained by the limited database resources and sample size, which may introduce potential bias in the results.