Tan Jiang-Shan, Liu Ningning, Guo Ting-Ting, Hu Song, Hua Lu, Qian Qiujin
State Key Laboratory of Cardiovascular Disease, Thrombosis Center, National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Peking University Sixth Hospital/Institute of Mental Health, Beijing, China.
Front Genet. 2022 Mar 16;13:743905. doi: 10.3389/fgene.2022.743905. eCollection 2022.
: This study was aimed to apply a Mendelian randomization design to explore the causal association between coronavirus disease 2019 (COVID-19) and three cardio-cerebrovascular diseases, including atrial fibrillation, ischemic stroke, and coronary artery disease. : Two-sample Mendelian randomization was used to determine the following: 1) the causal effect of COVID-19 on atrial fibrillation (55,114 case participants vs 482,295 control participants), coronary artery disease (34,541 case participants vs 261,984 control participants), and ischemic stroke (34,217 case participants vs 40,611 control participants), which were obtained from the European Bioinformatics Institute, and 2) the causal effect of three cardio-cerebrovascular diseases on COVID-19. The single-nucleotide polymorphisms (SNPs) of COVID-19 were selected from the summary-level genome-wide association study data of COVID-19-hg genome-wide association study (GWAS) meta-analyses (round 5) based on the COVID-19 Host Genetics Initiative for participants with European ancestry. The random-effects inverse-variance weighted method was conducted for the main analyses, with a complementary analysis of the weighted median and Mendelian randomization (MR)-Egger approaches. : Genetically predicted hospitalized COVID-19 was suggestively associated with ischemic stroke, with an odds ratio (OR) of 1.049 [95% confidence interval (CI) 1.003-1.098; = 0.037] in the COVID-19 Host Genetics Initiative GWAS. When excluding the UK Biobank (UKBB) data, our analysis revealed a similar odds ratio of 1.041 (95% CI 1.001-1.082; = 0.044). Genetically predicted coronary artery disease was associated with critical COVID-19, with an OR of 0.860 (95% CI 0.760-0.973; = 0.017) in the GWAS meta-analysis and an OR of 0.820 (95% CI 0.722-0.931; = 0.002) when excluding the UKBB data, separately. Limited evidence of causal associations was observed between critical or hospitalized COVID-19 and other cardio-cerebrovascular diseases included in our study. : Our findings provide suggestive evidence about the causal association between hospitalized COVID-19 and an increased risk of ischemic stroke. Besides, other factors potentially contribute to the risk of coronary artery disease in patients with COVID-19, but not genetics.
本研究旨在采用孟德尔随机化设计，探讨2019冠状病毒病（COVID-19）与三种心脑血管疾病（包括心房颤动、缺血性卒中和冠状动脉疾病）之间的因果关联。采用两样本孟德尔随机化来确定以下内容：1）COVID-19对心房颤动（55114例参与者与482295例对照参与者）、冠状动脉疾病（34541例参与者与261984例对照参与者）和缺血性卒中（34217例参与者与40611例对照参与者）的因果效应，这些数据来自欧洲生物信息学研究所；2）三种心脑血管疾病对COVID-19的因果效应。COVID-19的单核苷酸多态性（SNP）是从基于COVID-19宿主遗传学倡议的COVID-19-hg全基因组关联研究（GWAS）荟萃分析（第5轮）的汇总水平全基因组关联研究数据中选择的，用于欧洲血统的参与者。主要分析采用随机效应逆方差加权法，并对加权中位数和孟德尔随机化（MR）-Egger方法进行补充分析。在COVID-19宿主遗传学倡议GWAS中，遗传预测的住院COVID-19与缺血性卒中存在提示性关联，优势比（OR）为1.049[95%置信区间（CI）1.003-1.098；P=0.037]。排除英国生物银行（UKBB）数据后，我们的分析显示类似的优势比为1.041（95%CI 1.001-1.082；P=0.044）。遗传预测的冠状动脉疾病与重症COVID-19相关，在GWAS荟萃分析中的OR为0.860（95%CI 0.760-0.973；P=0.017），排除UKBB数据后的OR为0.820（95%CI 0.722-0.931；P=0.002）。在我们研究中纳入的重症或住院COVID-19与其他心脑血管疾病之间，观察到的因果关联证据有限。我们的研究结果为住院COVID-19与缺血性卒中风险增加之间的因果关联提供了提示性证据。此外，其他因素可能导致COVID-19患者患冠状动脉疾病的风险增加，但不是遗传因素。
