基于孟德尔随机化探索臀围与2型糖尿病的因果关系

  目的  采用孟德尔随机化分析方法, 探讨臀围与2型糖尿病的因果关联。  方法  将分别来自人体测量特征遗传研究(genetic investigation of anthropometric traits, GIANT)和糖尿病遗传学验证和荟萃分析(diabetes genetics replication and Meta-analysis, DIAGRAM)数据库的臀围和2型糖尿病遗传位点数据, 据单核苷酸多态性(single nucleotide polymorphism, SNP)编号匹配合并, 以与臀围密切相关的SNP为工具变量, 运用逆方差加权法、MR-Egger回归模型和加权中位数法分析臀围对2型糖尿病的因果效应。  结果  不分性别队列、女性队列和男性队列中分别匹配到52、9和15个SNP。异质性检验结果提示SNP间同质。三个队列的OR值及其95%的置信区间分别为1.065(1.030~1.100)、1.103(1.057~1.150)和1.583(1.273~1.968), 均有统计学意义(均有P < 0.05)。敏感性分析结果显示三个队列逐一移除SNP, 其因果效应不受影响, 结果稳健。  结论  人体臀围与2型糖尿病之间均存在因果关联, 臀围可能为2型糖尿病的危险因素。

Exploring the causal relationship between hip circumference and type 2 diabetes based on mendelian randomization

Objective To investigate the causal association between hip circumference(HC)and type 2 diabetes mellitus(T2DM)based on Mendelian randomization.Methods The genetic variants data of the HC and T2DM from the Genetic Investigation of Anthropometric Traits(GIANT)and DIAbetes Genetics Replication And Meta-analysis(DIAGRAM)database were matched according to the single nucleotide polymorphism(SNP)rsID.Genetic loci strongly related to the HC were used as instrumental variables;and the inverse-variance weighting,MR-Egger regression model and weighting median method were carried out to analyze the causal effect of HC on T2DM.Results Fifty-two,nine and fifteen SNPs were matched in the total cohort,female cohort and male cohort,respectively.Heterogeneity test suggested the SNPs were homogeneous.We found HC to be positively associated with T2DM risk(OR=1.065,95%CI:1.030-1.100,0R=1.103,95%CI:1.057-1.150 and OR=1.583,95%CI:1.273-1.968,respectively)in above three cohorts,respectively.Sensitivity analysis showed the results were robust.Conclusions There is a relationship between HC and T2DM of people,and HC may be the risk factor of T2DM.