双向两样本孟德尔随机化探究白细胞端粒长度与主动脉瘤发生风险的关系

Association between leukocyte telomere length and the risk of aortic aneurysm:A bidirectional two-sample Mendelian randomization study

目的采用双向两样本孟德尔随机化(Mendelian randomization,MR)方法探讨白细胞端粒长度(leukocyte telomere length,LTL)与主动脉瘤(aortic aneurysm,AA)发生风险的潜在因果关系。方法通过使用LTL和AA的最新全基因组关联研究(genome-wide association study,GWAS)公开数据库,找到LTL和AA相关的遗传变异位点作为工具变量(instrumental variable,IV),进行双向两样本MR分析,以逆方差加权法(inverse variance weighted,IVW)为主要方法分析LTL与AA之间的因果关系,应用Cochran's Q检验进行异质性分析,应用MR-Egger截距项探讨工具变量的潜在多效性,应用留一法(Leave-one-out,LOO)进行敏感性分析。结果基因预测更长的LTL对AA发生风险的降低显著相关,并且LOO分析显示结果稳定,而AA与LTL长度改变并无明显因果关系。结论研究结果提示,更长的LTL对AA具有保护作用,对患者进行LTL监测将有助于AA的早期筛查与预防。

Objective To investigate the potential causal relationship of leukocyte telomere length(LTL)with the risk of aortic aneurysm(AA)using a bidirectional two-sample Mendelian randomization(MR)study.Methods Based on latest public genome-wide association study(GWAS)databases of LTL and AA,genetic variants associated with the LTL and AA were selected as instrumental variables(IV)to perform a bidirectional two-sample MR study.The causal relationship of LTL with AA risk was mainly assessed by inverse-variance weighting(IVW)method.Heterogeneity was analyzed by the Cochran's Q test,the MR-Egger intercept was used to explore the potential pleiotropy of instrumental variables,and Leave-one-out(LOO)was used as sensitivity analysis.Results Genetically predicted that longer LTL was causally associated with the risk of AA,and LOO test showed that the results have robustness,while AA was not causally associated with the risk of LTL.Conclusion The MR study result indicated that longer LTL is protective against AA,hence,LTL monitoring of patients will be helpful for the early detection and prevention of AA.