一种转化基因组学方法将IL10RB鉴定为新冠病毒易感性的首要候选基因靶点。
A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility.
作者信息
Voloudakis Georgios, Vicari James M, Venkatesh Sanan, Hoffman Gabriel E, Dobrindt Kristina, Zhang Wen, Beckmann Noam D, Higgins Christina A, Argyriou Stathis, Jiang Shan, Hoagland Daisy, Gao Lina, Corvelo André, Cho Kelly, Lee Kyung Min, Bian Jiantao, Lee Jennifer S, Iyengar Sudha K, Luoh Shiuh-Wen, Akbarian Schahram, Striker Robert, Assimes Themistocles L, Schadt Eric E, Lynch Julie A, Merad Miriam, tenOever Benjamin R, Charney Alexander W, Brennand Kristen J, Fullard John F, Roussos Panos
机构信息
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
出版信息
NPJ Genom Med. 2022 Sep 5;7(1):52. doi: 10.1038/s41525-022-00324-x.
Recent efforts have identified genetic loci that are associated with coronavirus disease 2019 (COVID-19) infection rates and disease outcome severity. Translating these genetic findings into druggable genes that reduce COVID-19 host susceptibility is a critical next step. Using a translational genomics approach that integrates COVID-19 genetic susceptibility variants, multi-tissue genetically regulated gene expression (GReX), and perturbagen signatures, we identified IL10RB as the top candidate gene target for COVID-19 host susceptibility. In a series of validation steps, we show that predicted GReX upregulation of IL10RB and higher IL10RB expression in COVID-19 patient blood is associated with worse COVID-19 outcomes and that in vitro IL10RB overexpression is associated with increased viral load and activation of disease-relevant molecular pathways.
最近的研究已确定了与2019冠状病毒病（COVID-19）感染率和疾病结局严重程度相关的基因位点。将这些基因研究结果转化为可降低COVID-19宿主易感性的可成药基因是关键的下一步。通过整合COVID-19遗传易感性变异、多组织基因调控基因表达（GReX）和干扰因子特征的转化基因组学方法，我们确定IL10RB是COVID-19宿主易感性的首要候选基因靶点。在一系列验证步骤中，我们表明，COVID-19患者血液中预测的IL10RB基因调控基因表达上调和较高的IL10RB表达与更差的COVID-19结局相关，并且体外IL10RB过表达与病毒载量增加和疾病相关分子途径的激活有关。
Zotero 插件