ABSTRACT
[This corrects the article DOI: 10.3389/fpsyt.2021.746276.].
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.
ABSTRACT
Background: The outbreak of 2019 coronavirus disease (COVID-19) has become a global pandemic. Although it has long been suspected that COVID-19 could contribute to the development of mental illness, and individuals with a pre-existing mental illness may have a higher risk of and poorer outcomes from COVID-19 infection, no evidence has established a causal association between them thus far. Methods: To investigate associations in support of a causal association between the severity of COVID-19 and mental illnesses, we leveraged large-scale genetic summary data from genome-wide association study (GWAS) summary datasets, including attention-deficit/hyperactivity disorder (ADHD) (n = 55,374), schizophrenia (n = 77,096), bipolar disorder (n = 51,710), and depression (n = 173,005), based on a previous observational study. 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 and multiple sensitivity analyses assessing horizontal pleiotropy and removing outliers in two different COVID-19 databases. Results: The Mendelian randomization (MR) analysis indicated that ADHD [odds ratio (OR) = 1.297; 95% confidence interval (CI), 1.029-1.634; p = 0.028] increased the risk of hospitalization due to COVID-19. A similar association was obtained in MR sensitivity analyses of the weighted median. In addition, genetically predicted COVID-19 was significantly associated with schizophrenia (OR = 1.043; 95% CI, 1.005-1.082; p = 0.027). Conclusions: Although many studies have reported a causal relationship between COVID-19 and mental illness, our study shows that this increased risk is modest. However, considering the characteristics of ADHD that might further increase the individuals' vulnerability to being infected by COVID-19, the ongoing massive worldwide exposure to COVID-19, and the high burden of schizophrenia, we believe that it is necessary to offer preventative measures to these populations and to provide more evidence in understanding the neurological impact of COVID-19.