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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.
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?:doi
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10.1016/j.jinf.2020.11.031
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document_parses/pdf_json/3719e19491ee52ac62ec3eb5b9a656f2ded757bf.json
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document_parses/pmc_json/PMC7698677.xml.json
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Mendelian randomization analysis identified genes pleiotropically associated with the risk and prognosis of COVID-19
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