基于两样本孟德尔随机化研究血脂水平和子宫内膜异位症之间的关系

Causal Association Between Blood Lipid and Endometriosis:A Two-Sample Mendelian Randomization Analysis

目的 采用两样本孟德尔随机化研究,探索血脂水平和子宫内膜异位症之间的因果关系。方法 利用大样本全基因组关联研究(GWAS)汇总数据,选择与各类血脂水平密切相关的遗传位点为工具变量,采用逆方差加权法进行两样本孟德尔随机化分析,以OR值评价各类血脂水平与子宫内膜异位症间的因果关系。结果 除了极小极低密度脂蛋白(VLDL)胆固醇外,其余与VLDL有关的血脂水平升高会增加子宫内膜异位症的发病风险(OR>1)。高密度脂蛋白(HDL)中与胆固醇有关的血脂类型、小低密度脂蛋白(LDL)中总胆固醇水平升高可减少子宫内膜异位症的发病风险(OR<1)。所有与甘油三酯相关的血脂类型、小LDL中胆固醇酯与总脂质比率的升高均可增加子宫内膜异位症的发病风险(OR>1)。结论 多种类型的血脂水平会影响子宫内膜异位症的发生,HDL中与胆固醇或甘油三酯相关的血脂水平可作筛查子宫内膜异位症的生物指标。

Objective To explore the causal relationship between blood lipid and endometriosis using the two-sample Mendelian randomization(MR)analysis.Methods Genetic variants which were closely related to blood lipid in large sample genome-wide association study(GWAS)summary data were identified as instrumental variables(IV).Using odds ratio(OR)as outcome indicator,the causal relationship between blood lipid and endometriosis was analyzed by two-sample MR methods,including inverse variance weighted(IVW)method.Results Elevated levels of very low density lipoprotein(VLDL)related blood lipid increased the risk of endometriosis except very small VLDL cholesterol(OR>1).Elevated levels of cholesterol-related species in high density lipoprotein(HDL)were associated with a reduced risk of endometriosis(OR<1).Elevated levels of total cholesterol in small low density lipoprotein(LDL)were associated with a reduced risk of endometriosis(OR<1).Elevated levels of triglyceride-related species in HDL increased the risk of endometriosis(OR>1).An elevated ratio of cholesterol esters to total lipids in small LDL increased the risk of endometriosis(OR>1).Conclusion The study supports the impact of different blood lipid levels on the incidence of endometriosis,and suggests that cholesterol-related or triglyceride-related blood lipid levels in HDL should be used as biological indicators for endometriosis screening.