Mendelian randomization analysis identified genes pleiotropically associated with the risk and prognosis of COVID-19

medRxiv. 2020 Sep 4:2020.09.02.20187179. doi: 10.1101/2020.09.02.20187179. Preprint.


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 (Beta; [SE]=0.42 [0.09], P=4.75E-06 and Beta; [SE]=-0.48 [0.11], P=6.76E-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.

PMID:32909000 | PMC:PMC7480052 | DOI:10.1101/2020.09.02.20187179