6种代谢产物与特应性皮炎的因果关联:双向双样本孟德尔随机化研究  

Causal association between six metabolites and atopic dermatitis:a bidirectional two-sample Mendelian randomization study

作　　者：魏艳[1] 孙妍 王丽娟[1] 邵帅 郑焱 WEI Yan;SUN Yan;WANG Lijuan;SHAO Shuai;ZHENG Yan(Department of Dermatology,The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061;Department of Dermatology,The First Affiliated Hospital of Air Force Medical University,Xi’an 710032,China)

机构地区：[1]西安交通大学第一附属医院皮肤科,陕西西安710061 [2]空军军医大学第一附属医院皮肤科,陕西西安710032

出　　处：《西安交通大学学报（医学版）》2024年第5期801-808,共8页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.82273520,No.81972938);陕西省自然科学基础研究计划项目(No.2024JC-YBQN-0783);西安交通大学第一附属医院科研发展基金项目(No.2022QN-12)。

摘　　要：目的采用双向双样本孟德尔随机化(MR)分析来研究代谢产物与特应性皮炎(AD)之间的因果关系。方法从全基因组关联研究(GWAS)的汇总数据中提取与代谢产物相关的单核苷酸多态性(SNP)位点作为工具变量(IV)。使用R软件中的TwoSampleMR包对6种代谢物与AD之间的因果关联进行分析。所采用的主要方法包括逆方差加权法(IVW)、MR Egger和加权中位数法。使用Cochran’Q统计量进行异质性检验,MR Egger截距检验水平多效性,使用“留一法”进行敏感性分析。结果IVW分析结果显示,抗坏血酸(OR=0.861,95%CI:0.751~0.987)、花生四烯酸(OR=0.363,95%CI:0.193~0.683)、可的松(OR=0.447,95%CI:0.221~0.906)与AD的发生呈负相关;尿苷(OR=3.473,95%CI:1.043~11.562)、5-羟色胺(OR=1.896,95%CI:1.007~3.571)及2-羟基戊二酸(OR=2.158,95%CI:1.186~3.924)与AD的发生呈正相关,差异均具有统计学意义。结论遗传学预测的代谢产物与AD风险增加具有因果关联,但尚无显著证据支持AD与上述6种代谢产物之间的因果关系。Objective We made a bidirectional two-sample Mendelian randomization(MR)analysis to investigate the causal connection between metabolites and atopic dermatitis(AD).Methods Single nucleotide polymorphic(SNP)sites associated with metabolites were extracted from the aggregated data of a genome-wide association study(GWAS)as instrumental variables.Causal association between six metabolites and AD was analyzed using the TwoSampleMR package in R software.The primary methods employed included inverse variance weighted(IVW),MR Egger,and weighted median.Heterogeneity testing was conducted using Cochran’s Q statistics.MR Egger intercept was employed to test for level pleiotropy.Additionally,sensitivity analysis was carried out using the“leave-one-out”approach.Results The IVW analysis results indicated that ascorbic acid(OR=0.861,95%CI:0.751-0.987),arachidonic acid(OR=0.363,95%CI:0.193-0.683),and cortisone(OR=0.447,95%CI:0.221-0.906)were negatively correlated with the occurrence of AD,while uridine(OR=3.473,95%CI:1.043-11.562),serotonin(OR=1.896,95%CI:1.007-3.571),and 2-hydroxyglutaric acid(OR=2.158,95%CI:1.186-3.924)were positively correlated with the occurrence of AD,and the differences were statistically significant.Conclusion There is no significant evidence supporting a causal association between AD and metabolic disorder,but this study identified potential evidence for a causal effect of six metabolic factors on an increased risk of AD.

关 键 词：特应性皮炎(AD) 孟德尔随机化(MR) 因果关联 代谢产物 逆方差加权法(IVW) 

分 类 号：R751[医药卫生—皮肤病学与性病学]