两样本孟德尔随机化法分析儿童期肥胖与成人深静脉血栓形成的因果关联

Two-sample Mendelian randomization method to analyze the causal association between childhood obesity and adult deep vein thrombosis

目的采用孟德尔随机化法探究儿童期肥胖与成人深静脉血栓形成发病风险的因果关联。方法基于儿童期肥胖和深静脉血栓形成的全基因组关联研究数据库,筛选出5个相关的单核苷酸多态性位点(参数为P<5×10-8、连锁不平衡r2<0.1),通过逆方差加权法(inverse-variance weighted,IVW)、加权中位数法和MR-Egger回归法等统计方法,对儿童期肥胖与成人深静脉血栓形成之间的因果关系进行研究。结果IVW分析结果显示,儿童期肥胖是成人深静脉血栓的危险因素(OR=1.004,95%CI=1.002~1.006,P=0.000218),加权中值法(OR=1.004,95%CI=1.001~1.006,P=0.004)和MR-Egger回归法(OR=1.004,95%CI=1.002~1.029,P=0.011)分析也有相似的结果。敏感性分析显示遗传多效性不会对结果造成偏倚。结论两样本孟德尔随机化分析结果显示儿童期肥胖与成人深静脉血栓形成的发病风险存在正向因果关系。

Objective To explore the causal relationship between childhood obesity and the risk of adult deep vein thrombosis by using Mendelian randomization.Methods Based on the genome-wide association research databases of childhood obesity and deep vein thrombosis,five single nucleotide polymorphism sites were selected(parameter P<5×10-8,linkage disequilibrium r2<0.1).We used inverse variance weighting(IVW),weighted median method and MR-Egger regression method and to study the causal relationship between childhood obesity and adult deep vein thrombosis.Results IVW analysis showed that childhood obesity is a risk factor for adult deep vein thrombosis (OR=1.004,95%CI=1.002~1.006,P=0.000218),and the analysis results of weighted median method(OR=1.004,95%CI=1.001~1.006,P=0.004)and MR-Egger regression(OR=1.004,95%CI=1.002~1.029,P=0.011)were similar.The sensitivity analysis showed that genetic pleiotropy would not bias the results.Conclusion The results of Mendelian randomization analysis of two samples shows that there is a positive causal relationship between childhood obesity and the risk of adult deep vein thrombosis.