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Front Genet ; 13: 743905, 2022.
Article in English | MEDLINE | ID: covidwho-1775658

ABSTRACT

Aims: 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. Methods: 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. 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 GWAS. When excluding the UK Biobank (UKBB) data, our analysis revealed a similar odds ratio 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 an 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. Conclusion: 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.

2.
Pregnancy Hypertens ; 26: 17-23, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1364411

ABSTRACT

AIMS: The aim of this study was to apply the Mendelian randomization (MR) design to explore the potential causal association between COVID-19 and the risk of hypertension disorders in pregnancy. METHODS: Our primary genetic instrument comprised 8 single-nucleotide polymorphisms (SNPs) associated with COVID-19 at genome-wide significance. Data on the associations between the SNPs and the risk of hypertension disorders in pregnancy were obtained from study based on a very large cohort of European population. 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: Using IVW, we found that genetically predicted COVID-19 was significantly positively associated with hypertension disorders in pregnancy, with an odds ratio (OR) of 1.111 [95% confidence interval (CI) 1.042-1.184; P = 0.001]. Weighted median regression also showed directionally similar estimates [OR 1.098 (95% CI, 1.013-1.190), P = 0.023]. Both funnel plots and MR-Egger intercepts suggest no directional pleiotropic effects observed. CONCLUSIONS: Our findings provide direct evidence that there is a shared genetic predisposition so that patients infected with COVID-19 may be causally associated with increased risk of hypertension disorders in pregnancy.


Subject(s)
COVID-19/genetics , Genetic Predisposition to Disease , Hypertension/etiology , Mendelian Randomization Analysis/methods , Polymorphism, Single Nucleotide , Risk Assessment/methods , SARS-CoV-2 , COVID-19/complications , COVID-19/epidemiology , Female , Global Health , Humans , Hypertension/epidemiology , Hypertension/genetics , Incidence , Pregnancy , Risk Factors
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