Mendelian randomization analysis identified genes pleiotropically associated with the risk and prognosis of COVID-19 - 19/01/21
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Highlights |
• | We aimed to identify genes that were pleiotropically/potentially causally associated with COVID-19. |
• | We adopted a summary data-based Mendelian randomization method integrating summarized GWAS data for COVID-19 and cis- eQTL (expression quantitative trait loci) data. |
• | We identified 2 probes, ILMN_1,765,146 and ILMN_1,791,057 tagging IFNAR2, that showed pleiotropic association with hospitalized COVID-19. |
• | Multiple genes as tagged by the top 5 probes were involved in inflammation or antiviral immunity. |
• | Several other tagged genes, such as PON2 and HPS5, were involved in blood coagulation. |
Summary |
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.
Le texte complet de cet article est disponible en PDF.Keywords : Coronavirus disease 2019, IFNAR2, Gene expression quantitative trait loci, Summary Mendelian randomization
Plan
Vol 82 - N° 1
P. 126-132 - janvier 2021 Retour au numéro
Article précédent
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