目的 采用两样本孟德尔随机化(Mendelian randomization,MR)分析的方法研究血脂四项[甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)和低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)]与子宫平滑肌瘤(uterine leiomyoma,UL)的因果关系.方法 从 IEU open GWAS数据库获取UL及血脂四项的全基因组关联研究(GWAS)数据,筛选出与血脂四项强相关的单核苷酸多态性作为工具变量,使用逆方差加权法(inverse variance weighted,IVW)等进行两样本MR分析.然后对血脂四项与UL进行反向MR分析以评估两者是否存在反向因果关系.结果 IVW法显示TG与UL发病风险呈负相关(OR=0.996,95％CI:0.994～0.998,P＜0.001),HDL-C 与 UL 发病风险呈正相关(OR=1.002,95％CI:1.000～1.003,P=0.012),TC、LDL-C与UL发病无相关性(P＞0.05),反向MR分析未见血脂四项与UL存在反向因果关系(P＞0.05).以上的研究均未发现水平多效性(P＞0.05).结论 人体内TG的水平与UL的发病呈负相关,HDL-C的水平与UL的发病呈正相关,血脂四项与UL不存在反向因果关系.
Exploring the causal relationship between four lipid parameters and uter-ine leiomyoma based on two-sample Mendelian randomization
Objective To investigate the causal relationship between four lipid parameters-triglycerides(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)—and uterine leiomyoma(UL)using a two-sample Mendelian randomization(MR)analysis approach.Methods Genome-wide association study(GWAS)data for UL and the four lipid parameters were obtained from the IEU open GWAS database.Single nucleotide poly-morphisms(SNPs)strongly associated with the lipid parameters were selected as instrumental variables.Two-sample MR analyses were conducted using methods such as inverse variance weighted(IVW)analysis.Subsequently,reverse MR analysis was performed to assess whether there was a reverse causal relationship between the lipid parameters and UL.Results The IVW method indicated a negative correlation between TG and the risk of UL(OR=0.996,95％CI:0.994-0.998,P＜0.001)and a positive correlation between HDL-C and the risk of UL(OR=1.002,95％CI:1.000-1.003,P=0.012).No correlation was found be-tween TC or LDL-C and the incidence of UL(P＞0.05).Reverse MR analysis did not reveal any reverse causal relationship be-tween the lipid parameters and UL(P＞0.05).No horizontal pleiotropy was detected in the above studies(P＞0.05).Conclusion The level of TG in the body is negatively correlated with the incidence of UL while the level of HDL-C is positively correlated with the incidence of UL There is no reverse causal relationship between the four lipid parameters and UL.
NETL
NSTL
万方数据
