系统性红斑狼疮与心力衰竭：两样本孟德尔随机化研究

目的 系统性红斑狼疮(systemic lupus erythematosus, SLE)与心力衰竭之间的关系已受广泛关注，但观察性研究中二者的因果关联是不清楚的，因此本研究旨在使用两样本孟德尔随机化(Mendelian randomization, MR)研究来探究SLE和心力衰竭之间的因果关联。方法 从全基因组关联研究(Genome-wide association study, GWAS)汇总数据中提取与SLE相关的单核苷酸多态性(single nucleotide polymorphisms, SNPs),并选择符合标准的工具变量。然后，主要用逆方差加权法(inverse variance-weighted, IVW)进行两样本孟德尔随机化分析，并用MR-PRESSO、加权中值法、MR-Egger法和最大似然比来评估结果的稳健性。另外采用MR-Egger截距项评估工具变量的水平多效性，Cochran Q检验及留一法用来评估异质性。此外，多变量MR研究被用于进一步验证结果的稳健性。结果 IVW结果显示SLE的遗传易感性与心力衰竭相对风险增加呈正相关(OR=1.024, 95%CI...

Systemic lupus erythematosus and heart failure: a two-sample Mendelian randomization study

Objective To explore the causal relationship between systemic lupus erythematosus(SLE)and heart failure by two-sample Mendelian randomization(MR). Methods Single nucleotide polymorphisms(SNPs)associated with SLE were extracted from genome-wide association studies(GWAS), and a instrumental variable that met the criteria was selected. Then, the inverse variance-weighted(IVW)was used to conduct Mendelian randomization analysis, and the robustness of the result was assessed by weighted median, MR-PRESSO, MR-Egger method, and maximum likelihood ratio. In addition, the MR-Egger intercept test was performed to assess the horizontal pleiotropy of instrumental variables. Cochran Q test and leave-one-out method were conducted to evaluate the heterogeneity. Furthermore, a multivariate MR study was used to further verify the robustness of the results. Results The result of IVW showed a positive association between genetic predisposition of SLE and an increased relative risk of heart failure(OR=1.024, 95%CI: 1.001-1.048). Maximum likelihood ratio(OR=1.024, 95%CI: 1.003-1.046)showed consistent result and it was further confirmed by the multivariate MR study. Additionally, horizontal pleiotropy and heterogeneity were not observed by the MR-Egger intercept, Cochran Q test and the leave-one-out method. Conclusion SLE may increase the risk of heart failure, and aggressive control of SLE is recommended to reduce the risk of heart failure.