基于孟德尔随机化分析研究儿童肥胖与妊娠期糖尿病的因果关系及性激素结合球蛋白的调节作用

Study of the mediating effect of sex hormone-binding globulin on the causal association of childhood obesity and gestational diabetes based on Mendelian randomization analysis

目的:探讨儿童肥胖与妊娠期糖尿病(GDM)之间的独立因果关系,并确定性激素结合球蛋白(SHBG)对这一关系的中介作用。方法:利用全基因组关联研究(GWAS)对儿童肥胖和GDM的统计数据进行了双样本孟德尔随机化分析,评估儿童肥胖与GDM的因果影响,并通过中介分析研究儿童肥胖和GDM之间的关联是否通过性激素结合球蛋白发挥作用。结果:单变量孟德尔随机化结果显示,儿童肥胖可显著增加GDM的风险,儿童肥胖与SHBG呈负相关,SHBG与GDM呈负相关。多因素孟德尔随机化分析显示,儿童肥胖是GDM的独立危险因素,SHBG并非是GDM的独立危险因素。中介效应分析显示,SHBG是儿童肥胖所致的GDM的中介因子。结论:儿童期肥胖对GDM发病存在因果关系,SHBG可部分调控儿童肥胖导致的GDM发生。

Objective:To explore the independent causal relationship between childhood obesity and gestational diabetes mellitus(GDM)and to determine the mediating role of sex hormone-binding globulin(SHBG)in mediating this relationship.Methods:A two-sample Mendelian randomization was performed on the statistical data of childhood obesity and gestational diabetes using genome-wide association studies(GWAS)to estimate the causal effect of childhood obesity on gestational diabetes and to examine whether the association between childhood obesity and GDM acts through sex hormone-binding globulin.Results:Univariate Mendelian randomization results showed that childhood obesity could significantly increase the risk of GDM,while childhood obesity was inversely associated with SHBG,while SHBG was negatively associated with GDM.Multivariate Mendelian randomization analysis showed that childhood obesity is an independent risk factor for GDM,and SHBG is not an independent risk factor for gestational diabetes.Analysis of the mediation effect has shown that SHBG is a mediator of GDM due to childhood obesity.Conclusion:Childhood obesity has a causal relationship with the pathogenesis of GDM,and SHBG can partially regulate the occurrence of gestational diabetes caused by childhood obesity.