Mendelian randomization analysis identified genes pleiotropically associated with the risk and prognosis of COVID-19.
Mendelian randomization analysis identified genes pleiotropically associated with the risk and prognosis of COVID-19.
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DOI：
10.1016/j.jinf.2020.11.031
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Liu D;Yang J;Feng B;Lu W;Zhao C;Li L
2019冠状病毒病（COVID-19）已引发全球大流行。COVID-19患者在疾病行为上表现出相当大的差异。之前的全基因组关联研究已经确定了与COVID-19风险和预后相关的潜在遗传变异，但其潜在的生物学解释在很大程度上仍不清楚。我们采用基于汇总数据的孟德尔随机化（SMR）方法来鉴定与COVID-19风险和各种结果相关的基因，包括严重呼吸道确诊的COVID-19和住院的COVID-19。在血液中，我们发现标记IFNAR2的2个探针ILMN_1765146和ILMN_1791057与住院患者的COVID-19呈多向相关性（β [SE]=0.42 [0.09], P = 4.75 × 10−06,β [SE]=-0.48 [0.11], P = 6.76 × 10−06）。虽然校正后在血液和肺中多次检测后没有其他探针明显，但前5个探针标记的多个基因参与炎症或抗病毒免疫，其他几个标记的基因，如PON2和HPS5，参与血液凝固。我们确定了IFNAR2和其他可能参与COVID-19易感性或预后的潜在基因。这些发现为更好地理解COVID-19中细胞因子风暴和静脉血栓栓塞的机制以及有效治疗COVID-19的潜在治疗靶点提供了重要线索。
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. 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. 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. 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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影响因子：
158.5
作者：
Li, Qun;Guan, Xuhua;Feng, Zijian
通讯作者：
Feng, Zijian
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
56.9
作者：
MULLER, U;STEINHOFF, U;AGUET, M
通讯作者：
AGUET, M
影响因子：
28.3
作者：
Gorbalenya, Alexander E.;Baker, Susan C.;Ziebuhr, John
通讯作者：
Ziebuhr, John
影响因子：
9.8
作者：
Lloyd-Jones, Luke R.;Holloway, Alexander;Powell, Joseph E.
通讯作者：
Powell, Joseph E.