基于孟德尔随机化的血脂与糖尿病肾脏疾病因果关系的研究

    Causal relationship between blood lipids and diabetic kidney disease: a Mendelian randomization study

    • 摘要: 目的 利用大规模人群全基因组关联研究的汇总数据,通过孟德尔随机化分析探究血脂与糖尿病肾脏疾病(diabetic kidney disease,DKD)之间的关系。方法 利用逆方差加权法、加权中位数法、孟德尔随机化-Egger回归法对三酰甘油(triglyceride,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白(high density lipoprotein,HDL)、低密度脂蛋白(low density lipoprotein,LDL)与DKD的因果关系进行孟德尔随机化分析。以OR值和95%CI评价TG、TC、HDL、LDL等血脂指标与DKD风险的因果关系。其次进行敏感性分析来验证结果的可靠性,使用Cochran Q检验异质性,孟德尔随机化-Egger-截距检验是否存在水平多效性,Steiger检验方向性,留一法分析确定是否具有潜在影响的单核苷酸多态性等。结果 逆方差加权法作为主要分析方法,其分析结果显示,遗传预测的TG(OR=1.428,95%CI:1.150~1.774,P=0.001)、TC(OR=0.683,95%CI:0.486~0.960,P=0.028)与DKD存在因果关系,HDL(OR=0.879,95%CI:0.707~1.092,P=0.244)、LDL(OR=0.911,95%CI:0.698~1.191,P=0.496)没有证据可以证明其与DKD存在因果关系。结论 TG、TC在DKD发病中可能发挥作用,而没有证据证明HDL、LDL在DKD的发病中发挥作用。

       

      Abstract: Objective To explore the causal relationship between blood lipids and diabetic kidney disease(DKD)by a Mendelian randomization(MR)analysis using the summary data of large-scale population genome-wide association studies (GWAS). Methods Using inverse variance weighting method(IVW),weighted median method and MR-Egger regression method,the causal relationship of triglyceride(TG),total cholesterol(TC),high density lipoprotein(HDL),and low density lipoprotein (LDL)with DKD was analyzed by MR,and evaluated by odds ratio(OR)and 95% confidence interval (CI). Sensitivity analysis was performed to verify the reliability of the results. Cochran Q test was used to test heterogeneity,and MR-Egger-intercept test was used to test whether there was horizontal pleiotropic effect. Steiger test was used to test directionality,and leave-one-out analysis was used to determine whether there was potential single nucleotide polymorphism. Results The IVW method was used as the main analysis method. The analysis results showed that the genetic prediction of TG(OR=1. 428, 95%CI:1. 150-1. 774,P=0. 001)and TC(OR=0. 683,95%CI:0. 486-0. 960,P=0. 028)had a causal relationship with DKD. HDL (OR=0. 879,95%CI:0. 707-1. 092,P=0. 244) and LDL (OR=0. 911, 95%CI:0. 698-1. 191,P=0. 496)had no evidence to prove their causal relationship with DKD. Conclusion TG and TC may play a role in the pathogenesis of DKD,but there is no evidence that HDL and LDL play a role in the pathogenesis of DKD.

       

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