孟德尔随机化研究无麸质饮食与类风湿关节炎的相关性

Mendelian randomization study on the correlation between gluten free diet and rheumatoid arthritis

目的评价无麸质饮食(GFD)与类风湿关节炎(RA)的相关性。方法从大规模全基因组关联研究(GWAS)中获取数据,选择相互独立且与欧洲血统人群GFD及RA相关的遗传位点作为工具变量。GFD GWAS数据包括64949名个体和9851867名对照者。从GWAS中获取58284例RA患者及13108512名对照者数据。利用逆方差加权法(IVW)、MR Egger及加权中位数法和加权模式进行了两样本孟德尔随机化(MR)分析,对GFD与RA的相关性进行探讨。应用CochranQ检验及孟德尔随机多态性残差和离群值(MR-PRESSO)检测评估单核苷酸多态性(SNPs)的异质性。应用MR-Egger截距测试检验SNP的水平多效性。"留一法"敏感性分析评价MR研究是否受单个SNP的影响。结果在GFD与RA数据匹配后,3个SNP作为工具变量纳入研究。IVW显示GFD可显著降低RA的风险(β=-60.83,s_(x)=3.82,P<0.001)。加权中位数法及加权模式同样显示无麸质饮食可以降低RA的风险(β=-57.97,s_(x)=4.41,P<0.001;β=-55.81,s_(x)=5.10,P=0.008)。对其进行敏感性分析,GFD与RA相关性的敏感性分析显示SNP之间可能存在异质性(CochranQ检验,Q=12.80,P=0.002);MR-PRESSO结果显示未检测到异常的SNP(P=0.174)。森林图显示与GFD和RA密切相关的SNP具有稳定性。方法比较图显示多种检验方法结果基本一致。漏斗图显示SNP基本对称,提示MR分析没有多效性。MR Egger截距测试显示MR分析无水平多效性(截距值为-0.24,P=0.174)。"留一法"敏感性分析提示没有单个SNP对整体结果有较大影响。结论GFD与RA的风险降低有显著相关性。

Objective To evaluate the relationship between gluten-free diet and rheumatoid arthritis(RA).Methods Data were obtained from large-scale genome-wide association studies(GWAS),and genetic loci that are independent of gluten-free diet and RA of people of Europe2 were selected as instrumental variables.The gluten-free diet GWAS data included 64949 individuals and 9851867 controls.Data were obtained from GWAS of 58284 RA patients and 13108512 controls.The inverse variance weighted(IVW),MR Egger,weighted median method and weighted model were used to conduct two sample Mendelian randomization(MR)analysis.Cochran Q test and mendelian randomness pleiotropy residual sum and outlier(MR-PRESSO)were used to assess SNP heterogeneity.Applying the MR Egger intercept to test the level pleiotropy of SNP.The sensitivity analysis of the"leave one method"that evaluates whether MR studies were influenced by a single SNP.Results After matching GFD and RA data,three SNPs were included as instrumental variables in the study.IVW showed that GFD could significantly reduce the risk of RA(β=-60.83,s_(x)=3.82,P<0.001).The weighted median method and weighted pattern also showed that the gluten free diet could reduce the risk of RA(β=-57.97,s_(x)=4.41,P<0.001;β=-55.81,s_(x)=5.10,P=0.008).Sensitivity analysis of the correlation between GFD and RA showed that there might be heterogeneity between SNPs(Cochran Q test,Q=12.80,P=0.002).The MR-PRESSO results showed that no abnormal SNP was detected(P=0.174).The forest map showed that SNPs was closely related to GFD and RA stability.The method comparison chart showed that the results of multiple testing methods were basically consistent.The funnel plot showed that SNPs were basically symmetrical,indicating that there was no pleiotropy in MR analysis.The MR Egger intercept test showed no horizontal pleiotropy in MR analysis(intercept value was-0.24,P=0.174).The sensitivity analysis of the"leave one method"is suggested that no single SNP had a significant impact on the overall results.Conclusion Gluten free diet is related to the risk reduction of RA.