基于孟德尔随机化探究子宫内膜异位症与心血管疾病间的因果关系

    Explore the relationship between endometriosis and cardiovascular disease based on Mendelian randomization

    • 摘要:
      目的 采用双向两样本孟德尔随机化方法探究子宫内膜异位症(endometriosis,EMs)与心血管疾病(cardiovascular disease,CVD)间的因果关系。
      方法 基于全基因组关联研究中的汇总数据,以逆方差加权法(inverse variance weighting,IVW)为主要分析方法,以MR-Egger回归、加权中位数法、简单模型、加权模型为辅助分析方法,使用遗传变异为工具变量,分析EMs与6种常见CVD(包括:心绞痛、心肌梗死、冠心病、心力衰竭、心脏肥大、高血压)间的因果关系。进一步通过Cochran’s Q检验、MR-egger回归和留一法进行敏感性分析,以检验工具变量的异致性、水平多效性和稳健性。同时,用类似的方法分析以上6种CVD对EMs的影响,以探究可能存在的反向因果关系。
      结果 IVW分析结果显示,EMs对心绞痛(OR = 1.11,95% CI: 1.02~1.21,P<0.05)、心肌梗死(OR = 1.10,95% CI: 1.02~1.17,P<0.01)和冠心病(OR = 1.08,95% CI:1.01~1.15,P<0.05)的发病风险存在因果效应。Cochran’s Q检验、MR-egger回归和留一法的结果均表明结果具有稳健性。以上6种CVD对EMs均未显示出因果效应。
      结论 子宫内膜异位症对心绞痛、心肌梗死和冠心病具有正向因果效应。

       

      Abstract:
      AIM To explore the causal relationship between endometriosis (EMs) and cardiovascular disease (CVD) using bidirectional two-sample Mendelian randomization method.
      METHODS Based on the summary data from genome-wide association studies, inverse variance weighting (IVW) was used as the main analysis method, MR-Egger regression, weighted median estimation, simple model and weighted model were used as auxiliary analysis methods, and genetic variants were used as instrumental variables to analyze the association between EMs and 6 common CVD (including: angina pectoris, myocardial infarction, coronary heart disease, heart failure, cardiac hypertrophy, hypertension). Sensitivity analysis was further performed by Cochran's Q test, MR-egger regression, and leave-one-out method to test the heterogeneity, horizontal pleiotropy and robustness of instrumental variables. At the same time, the effects of the above 6 CVD on EMs were analyzed by similar methods to explore the possible reverse causality.
      RESULTS IVW analysis showed that EMs was significantly associated with angina pectoris (OR = 1.11, 95% CI: 1.02~1.21, P<0.05), myocardial infarction (OR = 1.10, 95% CI: 1.02~1.17, P<0.01) and coronary heart disease (OR = 1.08, 95% CI: 1.01~1.15, P<0.05). The results of Cochran's Q test, MR-egger regression and leave-one-out method showed that the results were robust. None of the above six CVD showed causal effect on EMs.
      CONCLUSION Endometriosis has positive causal effects on angina pectoris, myocardial infarction, and coronary heart disease.

       

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