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。
Causal relationship between blood lipids and diabetic kidney disease:a Mendelian randomization study
Objective To explore the causal relationship between blood lipids and diabetic kid-ney 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 pleio-tropic effect.Steiger test was used to test directionality,and leave-one-out analysis was used to deter-mine 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 re-lationship 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.Conclu-sion 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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