AUTHOR=Tan Jiang-Shan , Liu Ningning , Guo Ting-Ting , Hu Song , Hua Lu , Qian Qiujin 

TITLE=Genetic Predispositions Between COVID-19 and Three Cardio-Cerebrovascular Diseases

JOURNAL=Frontiers in Genetics

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.743905

DOI=10.3389/fgene.2022.743905

ISSN=1664-8021

ABSTRACT=Aims This study was aimed to apply a Mendelian randomization (MR) design to explore the causal association between Coronavirus Disease 2019 (COVID-19) and 3 cardio-cerebrovascular diseases, including atrial fibrillation, ischemic stroke, and coronary artery disease.
Methods Two-sample Mendelian randomization was used to determine: (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 3 cardio-cerebrovascular diseases on COVID-19. The SNPs of COVID-19 were selected from the summary-level GWAS data of COVID-19-hg 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 MR-Egger approaches.
Results 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; P=0.037] in the COVID-19 Host Genetics Initiative genome-wide association study (GWAS). When excluding the UK Biobank (UKBB) data, our analysis revealed a similar OR of 1.041 [95% CI 1.001–1.082; P=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; P=0.017] in the GWAS meta-analysis and OR of 0.820 [95% CI 0.722–0.931; P=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.
Conclusions Our findings provide suggestive evidence about the causal association between hospitalized COVID-19 and an increased risk of ischemic stroke. Besides, it is potentially other factors contribute to the risk of coronary artery disease in patients with COVID-19, but not genetics.