基于两样本孟德尔随机化研究血脂水平与翼状胬肉的因果效应

Causal effect between blood lipids level and pterygium based on a two-sample Mendelian randomization study

目的应用两样本孟德尔随机化(MR)研究探讨血脂水平与翼状胬肉的因果关系。方法以逆方差加权法(IVW)作为评估因果效应的主要检验方法,辅以MR-Egger回归和加权中位值(WM)作为补充检验方法。并通过Cochran's Q检验、MR-Egger回归的截距、MR-PRESSO方法和留一法进行敏感性分析。研究总胆固醇(TC)、低密度脂蛋白(LDL)、三酰甘油(TAG)和高密度脂蛋白(HDL)水平与翼状胬肉疾病的因果效应。结果TC水平与翼状胬肉存在正向因果关系(OR=1.983,95%CI:1.3682.873,P=0.003)。LDL水平与翼状胬肉存在正向因果关系(OR=1.818,95%CI:1.2052.745,P=0.004)。TAG和HDL水平与翼状胬肉间无因果关系(P>0.05)。Cochran's Q检验显示,TC、LDL和HDL的SNP间无异质性(P TC=0.888,P LDL=0.588,P HDL=0.097),TAG的SNP间存在异质性(P=0.024)。MR-PRESSO检验显示,TC、LDL和HDL不存在多效性(P TC=0.876,P LDL=0.612,P HDL=0.103),TAG存在多效性(P=0.020)。留一法分析显示,TC和LDL的结果稳健,HDL和TAG的结果缺乏稳健性。结论TC和LDL水平升高可能与翼状胬肉发病风险增加密切相关。

Objective To study the causal effect between blood lipids level and pterygium based on a two-sample Mendelian randomization(MR).Methods Inverse variance weighting(IVW)method was used as the main test method to evaluate the causal effect,and MR-Egger regression and weighted median(WM)value were used as supplementary test methods.Sensitivity analysis was carried out by Cochran's Q test,intercept of MR-Egger regression,MR-PRESSO method and leave-one-out method.The causal effects of total cholesterol(TC),low density lipoprotein(LDL),triglyceride(TAG)and high-density lipoprotein(HDL)levels on pterygium were investigated.Results There was a positive causal relationship between TC level and pterygium(OR=1.983,95%CI:1.368-2.873,P=0.003).There was a positive causal relationship between LDL levels and pterygium(OR=1.818,95%CI:1.205-2.745,P=0.004).There was no causal relationship between TAG and HDL levels and pterygium(P>0.05).Cochran's Q test showed that there was no heterogeneity among SNPs of TC,LDL and HDL(P TC=0.888,P LDL=0.588,P HDL=0.097),but there was heterogeneity in SNPs of TAG(P=0.024).MR-PRESSO test showed that TC,LDL and HDL did not have pleiotropy(P TC=0.876,P LDL=0.612,P HDL=0.103),while TAG had pleiotropy(P=0.020).The leave-one-out analysis showed that the results of TC and LDL were robust,while the results of HDL and TAG were not robust.Conclusion Elevated TC and LDL levels may be closely associated with an increased risk of pterygium.