Abstract
Observational studies have reported that the severity of COVID-19 depends not only on physical conditions but also on socioeconomic status, including educational level. Because educational attainment (EA), which measures the number of years of schooling, is moderately heritable, we investigated the causal association of EA on the risk of COVID-19 severity using the Mendelian randomization (MR) approach. A two-sample MR analysis was performed using publicly available summary-level data sets of genome-wide association studies (GWASs). A total of 235 single-nucleotide polymorphisms (SNPs) were extracted as instrumental variables for the exposure of EA from the Social Science Genetic Association Consortium GWAS summary data of 766,345 participants of European ancestry. The effect of each SNP on the outcome of COVID-19 severity risk was obtained from the GWAS summary data of 1,059,456 participants of European ancestry gathered from the COVID-19 Host Genetics Initiative. Using inverse variance weighted method, our MR study shows that EA was significantly associated with a lower risk of COVID-19 severity (odds ratio per one standard deviation increase in years of schooling, 0.540; 95% confidence interval, 0.376–0.777, P = 0.0009). A series of sensitivity analyses showed little evidence of bias. In conclusion, we show for the first time using a two-sample MR approach the associations between higher EA and the lower risk of COVID-19 severity in the European population. However, the genetic or epidemiological mechanisms underlying the association between EA and the risk of COVID-19 severity remain unknown, and further studies are warranted to validate the MR findings and investigate underlying mechanisms.
Highlights
IntroductionThe coronavirus disease 2019 (COVID-19), caused by a novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), was originally reported as an outbreak of atypical pneumonia cases in Wuhan in the Hubei Province of China in December 2019
The coronavirus disease 2019 (COVID-19), caused by a novel coronavirus SARS-CoV-2, was originally reported as an outbreak of atypical pneumonia cases in Wuhan in the Hubei Province of China in December 2019
For the outcome data set of the risk of COVID-19 severity, the single-nucleotide polymorphisms (SNPs) were obtained from summary-level genome-wide association studies (GWASs) data of COVID-19-hg GWAS metaanalyses including 14 studies, but excluding the UK Biobank, with a total of 1,059,456 participants (4,792 very severe respiratory confirmed COVID-19 cases and 1,054,664 controls) of European ancestry by the COVID-19 Host Genetics Initiative [19] (Supplementary Table 1), which was released on January 18, 2021, and was publicly available [20]
Summary
The coronavirus disease 2019 (COVID-19), caused by a novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), was originally reported as an outbreak of atypical pneumonia cases in Wuhan in the Hubei Province of China in December 2019. Serious COVID-19 patients have pneumonia with hypoxia and may be critical with acute respiratory distress syndrome, pulmonary fibrosis, and other organ failures [2]. Observational studies report that the severity of COVID19 depends on physical conditions such as age, cardiovascular disease, and obesity [3,4,5,6,7,8] and on socioeconomic status (SES) indicators such as lower incomes and lower educational level among various populations [9,10,11,12]. Traditional observational studies lacking randomization designs are generally prone to bias by various factors, including confounders and reverse causations [13]
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