Purpose. Two-sample Mendelian randomization (MR) was conducted to assess the causal relationship between angina pectoris and gout. Material and Methods. Based on genome-wide association studies, single nucleotide polymorphisms (SNPs) that were closely associated with gout were selected from the UK Biobank–Neale Lab (ukb-a-107) as genetic instrumental variables. Considering that gout is characterized by elevated blood uric acid levels, SNPs related to blood uric acid levels were screened from BioBank Japan (bbj-a-57) as auxiliary gene instrumental variables. SNPs closely associated with angina pectoris onset were screened from the FINN dataset (finn-b-I9_ANGINA) as outcome variables. Two-sample MR was conducted, with inverse variance weighting (IVW) of the random effects model as the primary result, along with the weighted median method (WME) and the MR-Egger regression method. To further confirm the causal relationship between angina and gout incidence, a meta-analysis was conducted on the IVW results of the ukb-a-107 and bbj-a-57. Results. The odds ratios and 95% confidence intervals of the IVW, WME, and MR-Egger results of ukb-a-107 were (OR = 33.72; 95% CI: 2.07∼550.38), (OR = 57.94; 95% CI: 2.75∼1219.82), and (OR = 96.38; 95% CI: 0.6∼15556.93), respectively. The values of IVW and WME were 0.014 and 0.014 (both <0.05), respectively, indicating that the development of angina pectoris was significantly associated with the incidence of gout. The odds ratios and 95% confidence intervals of the IVW, WME, and MR-Egger about bbj-a-57 were (OR = 1.20; 95% CI: 1.07∼1.34), (OR = 1.19; 95% CI: 1.02∼1.38), and (OR = 1.30; 95% CI; 1.06∼1.60), respectively. The values of IVW, WME and MR-Egger were 0.001, 0.027 and 0.017 (all <0.05), respectively, indicating a significant correlation between angina and blood uric acid levels. Scatter plots of ukb-a-107 and bbj-a-57 showed that the causal association estimates of the IVW, MR-Egger, and weighted median methods were similar and that the MR results were accurate. Funnel plots and the MR-Egger intercept of ukb-a-107 and bbj-a-57 showed the absence of horizontal pleiotropy. The leave-out sensitivity analysis results of ukb-a-107 and bbj-a-57 are stable. The meta-analysis of IVW results for ukb-a-107 and bbj-a-57 showed (OR = 1.20; 95% CI: 1.07–1.34, ), confirming that gout characterized by high blood uric acid levels significantly increases the risk of angina attacks. Conclusions. This MR study found a clear causal relationship between angina pectoris and gout, which increases the risk of angina pectoris.

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基于二样本孟德尔随机化的心绞痛与痛风因果关系

目的。进行两样本孟德尔随机化（MR）来评估心绞痛和痛风之间的因果关系。材料与方法。基于全基因组关联研究，从英国生物银行-尼尔实验室（ukb-a-107）中选择与痛风密切相关的单核苷酸多态性（SNP）作为遗传工具变量。考虑到痛风的特点是血尿酸水平升高，从BioBank Japan (bbj-a-57)中筛选出与血尿酸水平相关的SNP作为辅助基因工具变量。从 FINN 数据集 (finn-b-I9_ANGINA) 中筛选出与心绞痛发作密切相关的 SNP 作为结果变量。进行双样本MR分析，以随机效应模型的逆方差加权（IVW）作为主要结果，同时采用加权中值法（WME）和MR-Egger回归法。为了进一步证实心绞痛与痛风发病之间的因果关系，对ukb-a-107和bbj-a-57的IVW结果进行了荟萃分析。结果。 ukb-a-107的IVW、WME和MR-Egger结果的比值比和95%置信区间为(OR = 33.72; 95% CI: 2.07∼550.38), (OR = 57.94; 95% CI: 2.75 ～1219.82）和（OR = 96.38；95% CI：0.6～15556.93）。 IVW和WME值分别为0.014和0.014（均<0.05），表明心绞痛的发生与痛风的发生显着相关。 bbj-a-57 的 IVW、WME 和 MR-Egger 的比值比和 95% 置信区间分别为 (OR = 1.20; 95% CI: 1.07∼1.34)、(OR = 1.19; 95% CI: 1.02∼分别为（1.38）和（OR = 1.30；95% CI；1.06∼1.60）。 IVW、WME和MR-Egger值分别为0.001、0.027和0.017（均<0.05），表明心绞痛与血尿酸水平之间存在显着相关性。 ukb-a-107和bbj-a-57的散点图显示IVW、MR-Egger和加权中位数方法的因果关联估计相似，并且MR结果是准确的。 ukb-a-107 和 bbj-a-57 的漏斗图和 MR-Egger 截距显示不存在水平多效性。 ukb-a-107和bbj-a-57的遗漏敏感性分析结果稳定。 ukb-a-107 和 bbj-a-57 IVW 结果的荟萃分析显示（OR = 1.20；95% CI：1.07–1.34，），证实以高血尿酸水平为特征的痛风会显着增加心绞痛发作的风险。结论。这项MR研究发现心绞痛和痛风之间存在明确的因果关系，从而增加了心绞痛的风险。