矿物质和膳食补充剂对先天缺牙的影响：双样本孟德尔随机化分析

Effects of Minerals and Dietary Supplements on Congenital Tooth Agenesis: A Two-Sample Mendelian Randomization Analysis

摘要: 目的：采用孟德尔随机化研究探讨先天缺牙与矿物质和膳食补充剂摄入的因果联系。方法：从全基因组关联研究(GWAS)数据库中筛选与矿物质和膳食补充剂摄入密切相关且相互独立的单核苷酸多态性(SNP)位点，均为欧洲人群。选择finn-b-K11_HYPO_ONLY作为结局相关的SNP，同样为欧洲血统的人群，包括246名的病例和218,546例的对照组。结果：因果关联分析中，钙、鱼油、葡萄糖胺、铁、硒和锌等可作为暴露因素候选集。铁补充剂是个保护因素，其他几种补充剂与先天缺牙没有因果关系。IVW和MR Egger回归显示结果没有异质性。Egger回归分析表明没有多效性。对补充剂摄入和先天缺牙进行反向MR，所得结果先天缺牙与钙、鱼油、葡萄糖胺、铁、硒和锌等补充剂摄入没有因果关系(P > 0.05)。结论：孟德尔随机化分析结果表明摄入铁补充剂与先天缺牙存在因果关联。摄入铁补充剂是先天缺牙的保护因素。

Abstract: Objective: This paper aims to investigate the causal link between congenital tooth agenesis and mineral/dietary supplement intake using Mendelian randomization. Methods: The genome-wide association study (GWAS) database was screened for single nucleotide polymorphism (SNP) that were closely associated with and independent of mineral and dietary supplement intake in European populations. Finn-b-K11_HYPO_ONLY was selected as the outcome-related SNP including 246 cases and 218,546 controls, which were derived from European ancestry population. Results: In the causal association analysis, calcium, fish oil, glucosamine, iron, selenium and zinc can be used as candidate sets of exposure factors. Iron supplement was a protective factor, and the other supplements showed no causal relationship with congenital tooth agenesis. IVW and MR Egger regression showed no heterogeneity. Egger regression analysis showed no pleiotropy. Reverse MR was performed on supplement intake and congenital tooth agenesis, which showed that there was no causal relationship between congenital tooth agenesis and the intake of supplements such as calcium, fish oil, glucosamine, iron, selenium and zinc (P > 0.05). Conclusion: Mendelian randomization analysis results suggest a causal association between iron supplement intake and congenital tooth agenesis. Intake of iron supplements was a protective factor against congenital tooth agenesis.