Abstract
Objectives: COVID-19 has caused a large global pandemic. Patients with COVID-19 exhibited considerable variation in disease behavior. Pervious genome-wide association studies have identified potential genetic variants involved in the risk and prognosis of COVID-19, but the underlying biological interpretation remains largely unclear.
Methods: We applied the summary data-based Mendelian randomization (SMR) method to identify genes that were pleiotropically associated with the risk and various outcomes of COVID-19, including severe respiratory confirmed COVID-19 and hospitalized COVID-19.
Results: In blood, we identified 2 probes, ILMN_1765146 and ILMN_1791057 tagging IFNAR2, that showed pleiotropic association with hospitalized COVID-19 (β [SE]=0.42 [0.09], P = 4.75 × 10 -06 and β [SE]=-0.48 [0.11], P = 6.76 × 10 -06 , respectively). Although no other probes were significant after correction for multiple testing in both blood and lung, multiple genes as tagged by the top 5 probes were involved in inflammation or antiviral immunity, and several other tagged genes, such as PON2 and HPS5, were involved in blood coagulation.
Conclusions: We identified IFNAR2 and other potential genes that could be involved in the susceptibility or prognosis of COVID-19. These findings provide important leads to a better understanding of the mechanisms of cytokine storm and venous thromboembolism in COVID-19 and potential therapeutic targets for the effective treatment of COVID-19.
Keywords: Coronavirus disease 2019; Gene expression quantitative trait loci; IFNAR2; Summary Mendelian randomization.
【저자키워드】 Coronavirus disease 2019, IFNAR2, Gene expression quantitative trait loci, Summary Mendelian randomization., 【초록키워드】 COVID-19, Treatment, coronavirus disease, Inflammation, Coronavirus disease 2019, Cytokine storm, coronavirus, Prognosis, susceptibility, mendelian randomization, Variation, lung, risk, Blood coagulation, cytokine, outcome, Venous Thromboembolism, Coagulation, global pandemic, Interpretation, Genome-wide association study, Genetic variant, respiratory, antiviral immunity, disease, expression, Quantitative, mechanism, Blood, association, IFNAR2, leads, correction, probes, potential therapeutic targets, potential therapeutic target, hospitalized COVID-19, probe, multiple testing, Genes, effective, SMR, HPS5, PON2, identify, caused, involved, applied, exhibited, pleiotropic, with COVID-19, 【제목키워드】 COVID-19, mendelian randomization, risk, Analysis,