广西医学

目的基于孟德尔随机化（MR）方法分析矿物质和维生素与炎症性肠病（IBD）之间的因果关联。方法从OpenGWAS数据库中获取多种矿物质和维生素的全基因组关联研究（GWAS）数据，分别从OpenGWAS数据库和GWASCatalog数据库获取克罗恩病（CD）和溃疡性结肠炎（UC）的GWAS数据。以矿物质和维生素作为暴露因素，CD和UC作为结局，以与矿物质和维生素显著相关的单核苷酸多态性（SNP）作为工具变量。采用逆方差加权（IVW）法作为主要方法，MR⁃Egger法、加权中位数（WME）法、简单模式（SM）法及加权模式（WM）法作为补充方法，分析矿物质和维生素与UC和CD之间的因果关联。采用Cochran's Q检验、MR⁃Egger回归截距分析和MR⁃PRESSO检验、留一法进行敏感性分析。结果共筛选出10个与维生素C紧密相关的SNP，IVW法分析显示维生素C与CD存在负向关联（OR<1，P<0.05），WME法分析结果同样支持该负向关联（P<0.05），MR⁃Egger法、SM法及WM法分析结果虽无统计学意义，但其效应方向（OR<1）与IVW法一致。共有6个与铜相关的SNP，铜与UC存在正向关联（OR>1，P<0.05），MR⁃Egger法、WME法、SM法及WM法分析结果虽无统计学意义，但其效应方向（OR>1）与IVW法一致。敏感性分析未发现明显异质性影响、水平多效性及单个SNP主导因果估值的情况。结论维生素C可能在CD发病机制中发挥重要作用，铜可能在UC发病机制中起关键作用。

Objective To analyze the causal association of minerals and vitamins with inflammatory bowel disease (IBD) based on the Mendelian randomization (MR) method. Methods Data of Genome⁃Wide Association Study (GWAS) for various minerals and vitamins were obtained from the OpenGWAS database. GWAS data for Crohn's disease (CD) and ulcerative colitis (UC) were acquired from the OpenGWAS and GWASCatalog databases, respectively. Minerals and vitamins served as exposures, CD and UC as outcomes, and single nucleotide polymorphism (SNP) significantly associated with minerals and vitamins as instrumental variables. The inverse variance weighted (IVW) method was used as the primary method, supplemented by the MR⁃Egger, weighted median (WME), simple mode (SM), and weighted mode (WM) methods to analyze the causal association of minerals and vitamins with UC and CD. Sensitivity analysis was conducted using Cochran's Q test, MR⁃Egger regression intercept analysis, MR⁃PRESSO test, and leave⁃one⁃out method. Results Ten SNPs closely related to vitamin C were identified. IVW analysis revealed that a negative correlation of vitamin C with CD (OR<1, P<0.05). WME also supported this negative correlation (P<0.05). Although there was no statistically significant difference in the results of the MR⁃Egger, SM, and WM methods, their effect directions (OR<1) were consistent with the IVW results. A total of 6 SNPs related to copper were identified, showing a positive correlation of copper on UC (OR>1, P<0.05). Although there was no statistically significant difference in results of the MR⁃Egger, WME, SM, and WM methods, their effect directions (OR>1) were consistent with the IVW results. Sensitivity analysis revealed no significant heterogeneity, horizontal pleiotropy, or undue influence of any single SNP on the causal estimates. Conclusion Vitamin C may play an important role in the pathogenesis of CD, and copper may play a key role in the pathogenesis of UC.