教育程度增加变应性鼻炎和(或)湿疹的患病风险:一项基于欧洲患者全基因组关联研究的孟德尔随机化研究

Educational attainment increases the risk of developing allergic rhinitis and(or)eczema:a Mendelian randomization study based on genome-wide association studies in European patients

目的采用孟德尔随机化(MR)方法探索教育程度与变应性鼻炎和(或)湿疹患病风险之间的因果关系。方法对基于大样本全基因组关联研究(GWAS)的汇总数据进行二次数据分析,包括来自社会科学基因组学会联盟的293723例参与者(教育程度)和来自英国生物样本库的462013例参与者[变应性鼻炎和(或)湿疹]。选择与教育程度密切相关的遗传位点作为工具变量,分别采用逆方差加权(IVW)、MR-Egger回归、加权中位数法和加权众数法进行两样本MR分析,以优势比(OR)评价教育程度与变应性鼻炎和(或)湿疹的患病风险之间的因果关联。结果共纳入70个单核苷酸多态性(SNPs)作为工具变量。MR-Egger回归结果显示,基因多效性不会对结果造成偏倚(P=0.107)。在单变量MR分析中,IVW结果显示,教育年限每增加1年或1个标准差(3.71年),患变应性鼻炎和(或)湿疹的风险分别为OR=1.044(95%CI:1.020~1.069,P<0.001)和OR=1.170(95%CI:1.074~1.256,P<0.001)。在反向MR分析中,IVW未观察到变应性鼻炎和(或)湿疹对教育年限的影响(OR=1.020,95%CI:0.927~1.023,P=0.683)。加权中位数法和加权众数法的结果与IVW的结果基本一致。结论教育程度与变应性鼻炎和(或)湿疹患病风险之间存在正向因果关系,即教育程度升高会增加变应性鼻炎和(或)湿疹的患病风险。

Objective To determine the causal relationship between educational attainment and the risk of allergic rhinitis and(or)eczema using Mendelian randomization(MR)analyses.Methods This study was a secondary data analysis based on the summary data of genome-wide association studies(GWAS),which involved 293723 participants(educational attainment)from the Social Science Genetics Association Consortium and 462013 participants[allergic rhinitis and(or)eczema]from the UK Biobank.Genetic variants that were closely related to educational attainment were identified as instrumental variables.Two-sample MR analyses,including inverse-variance weighted(IVW),MR-Egger regression,weighted median method and weighted model-based estimation,were performed to investigate the causal relationship between educational attainment and the risk of allergic rhinitis and(or)eczema,in which the odds ratio(OR)values were used as indicators.Results A total of 70 single-nucleotide polymorphisms(SNPs)were chosen as instrumental variables.The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results(P=0.107).In the univariable MR analyses,IVW regression showed that the risk of allergic rhinitis and(or)eczema was OR=1.044(95%CI:1.020-1.069,P<0.001)and OR=1.170(95%CI:1.074-1.256,P<0.001),respectively,for the increase in the duration of education by one year or one standard deviation(SD)(3.71 years).In the reverse MR analysis,IVW regression showed little evidence that allergic rhinitis and(or)eczema affected educational attainment(OR=1.020,95%CI:0.927-1.023,P=0.683).The results of the weighted median method and weighted mode-based estimation were consistent with the results of IVW.Conclusion This study suggests that there is a positive causal relationship between educational attainment and the risk of allergic rhinitis and(or)eczema,which means that educational attainment can increase the occurrence of allergic rhinitis and(or)eczema.