Causally Associations of Blood Lipids Levels with COVID-19 Risk: Mendelian Randomization Study (preprint)

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). It has been found that coronary artery disease (CAD) is a comorbid condition for COVID-19. As the risk factors of CAD, whether blood lipids levels are causally related to increasing susceptibility and severity of COVID-19 is still unknown. Design: We performed two-sample Mendelian Randomization (MR) analyses to explore whether dyslipidemia, low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), triglyceride (TG) and total cholesterol (TC) were causally related to COVID-19 risk and severity. The GWAS summary data of blood lipids involving in 188,578 individuals and dyslipidemia in a total of 53,991 individuals were used as exposures, respectively. Two COVID-19 GWASs including 1,221 infected patients and 1,610 severe patients defined as respiratory failure were employed as outcomes. Based on the MR estimates, we further carried out gene-based and gene-set analysis to explain the potential mechanism for causal effect. Results: The MR results showed that dyslipidemia was casually associated with the susceptibility of COVID-19 and induced 27% higher odds for COVID-19 infection (MR-IVW OR = 1.27, 95% CI 1.08 to 1.49, p-value = 3.18 x 10-3). Moreover, the increasing level of blood TC will raise 14 % higher odds for the susceptibility of COVID-19 (MR-IVW OR = 1.14, 95% CI 1.04 to 1.25, p-value = 5.07 x 10-3). Gene-based analysis identified that ABO gene was associated with TC and the gene-set analysis found that immune processes were involved in the risk effect of TC. Conclusions: We obtained three conclusions: 1) Dyslipidemia is casually associated with the susceptibility of COVID-19; 2) TC is a risk factor for the susceptibility of COVID-19; 3) The different susceptibility of COVID-19 in specific blood group may be partly explained by the TC concentration in diverse ABO blood groups.