基于双向孟德尔随机化分析探究豆制品与痛风的因果关系

Exploring the Causal Association between Soy Products Intake and Gout by Bidirectional Mendelian Randomization Analysis

摘要: 背景：大豆制品与痛风之间的因果关系尚未从遗传角度阐明。目的：本研究旨在通过双向两样本孟德尔随机化(MR)方法，探讨三种大豆制品(豆腐、豆浆和大豆甜点)摄入与痛风之间的遗传关联。方法：从已知的全基因组关联研究综合数据库中提取大豆制品相关单核苷酸多态性位点作为工具变量。RStudio中的TwoSampleMR软件包用于对大豆制品和痛风进行双向MR分析。MR分析使用了五种不同的方法：逆方差加权、MR-Egger回归、加权中值、简单模式和加权模式。使用异质性函数进行异质性检验，并通过MR Egger截距检验评估水平多效性。使用留一法进行敏感性分析，以验证结果的稳健性。结果：五种MR分析方法产生的P值均大于0.05。敏感性分析表明，既没有异质性也没有多效性，留一法分析结果表明，去除任何单个SNP都不会显著影响结果。结论：大豆制品摄入与痛风风险之间没有遗传关联。

Abstract: Background: The causal relationship between soy products and gout has not yet been clarified from a genetic perspective. Objective: This study aimed to explore the genetic association between three types of soy products (tofu, soya milk, and soya dessert) intake and gout, using a bidirectional two-sample Mendelian randomization (MR) approach. Methods: Soy product-related single nucleotide polymorphism loci were extracted as instrumental variables from the comprehensive database of known genome-wide association studies. The TwoSampleMR package in RStudio was used to carry out bidirectional MR analysis for soy products and gout. Five different methods were used for the MR analysis: inverse variance weighted, MR Egger regression, weighted median, simple mode, and weighted mode. Heterogeneity tests were conducted using the heterogeneity function, and horizontal pleiotropy was assessed by the MR-Egger intercept test. Sensitivity analysis was performed using the leave-one-out method to validate the robustness of the results. Results: The P-values generated by the five methods of MR analysis were all greater than 0.05. Sensitivity analysis indicated neither heterogeneity nor pleiotropy, and the leave-one-out method showed that removing any single SNP did not significantly affect the results. Conclusion: No genetic association was found between soy products intake and the risk of gout.