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| 孟德尔随机化法探究TGF-β与AAMI后左室舒张末容积的关系 |
| Investigation the relationship between TGF-β level and left ventricular volume after AAMI based mendelian randomization |
| 投稿时间：2022-09-20 |
| DOI：10.3969/j.issn.1000-0399.2023.05.007 |
| 中文关键词: 孟德尔随机化 转化生长因子-β 心肌梗死 左室舒张末容积 |
| 英文关键词: Mendelian randomization Transforming growth factor-β Myocardial infarction Left ventricular end-diastolic volume |
| 基金项目:安徽医科大学校基金青年项目（编号：2021xkj286） |
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| 中文摘要: |
| 目的 采用孟德尔随机化方法(MR)探究转化生长因子-β(TGF-β)水平与急性前壁心肌梗死(AAMI)急性期后左室舒张末容积(LVEDV)的因果关系。方法 从基因组和表观基因组关联研究(GWAS/EWAS)数据库选取 TGF-β 和 AAMI 后 LVEDV 数据。TGF-β 数据包括 982 例样本,LVEDV 数据包括 35 407 例样本。选择与 TGF-β 独立相关的显著基因位点作为工具变量,分别使用逆方差加权法(IVW)、加权中位数、加权模式法及 MR-Egger 回归研究 TGF-β 与 AAMI 急性期后 LVEDV 的关系。结果 逆方差加权法(IVW)法结果显示,TGF-β 升高能增加 AAMI 后 LVEDV 扩大的风险(OR=1.021,95%CI:1.007~1.035,P=0.004)。与加权中位数法(OR=1.017,95% CI:1.008~1.026,P=2.26×10-4)及加权模式法(OR=1.014,95%CI:1.000~1.028,P=0.043),结果一致。MR-Egger 回归截距为-0.002(95% CI:-0.018~0.014,P=0.791),表明工具变量几乎不存在多效性。散点图及漏斗图均提示,研究结果稳定可靠。结论 TGF-β 水平与 AAMI 急性期后 LVEDV 存在正向因果效应,即 TGF-β 升高能导致 AAMI 急性期后 LVEDV 扩大。 |
| 英文摘要: |
| Objective To investigate the causal relationship between transforming growth factor- β (TGF-β) level and left ventricular end-diastolic volume (LVEDV) after acute anterior myocardial infarction (AAMI) by Mendelian randomization (MR). Methods TGF-β and LVEDV data were selected from genome and epigenome association study (GWAS/EWAS) database. TGF-β data included 982 samples and LVEDV data included 35 407 samples. Significant loci independently associated with TGF-β were selected as instrumental variables, and MR analysis was performed using inverse variance weighted, weighted median, weighed mode and MR-Egger regression respectively. Results The inverse variance weighting (IVW) method showed that TGF-β increased risk of LVEDV expansion after AAMI (OR=1.021, 95%CI:1.007- 1.035, P=0.004). The conclusion of different methods was consistent:weighted median method (OR=1.017, 95% CI:1.008-1.026, P=2.26×10-4); weighted mode method(OR=1.014, 95%CI:1.000-1.028, P=0.043). The intercept of MR-Egger regression was -0.002 (95%CI:-0.018- 0.014, P=0.791), indicating that there was almost no pleiotropy in instrumental variables. Both scatter plot and funnel plot suggested that the results were stable and reliable. Conclusions There is a positive causal effect between TGF-β level and LVEDV after acute phase of AAMI, that is, the increase of TGF-β can lead to the expansion of LVEDV after acute phase of AAMI. |
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