Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA.
Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, China.
Genet Med. 2021 Nov;23(11):2076-2086. doi: 10.1038/s41436-021-01243-5. Epub 2021 Jun 28.
It is critical to identify putative causal targets for SARS coronavirus 2, which may guide drug repurposing options to reduce the public health burden of COVID-19.
We applied complementary methods and multiphased design to pinpoint the most likely causal genes for COVID-19 severity. First, we applied cross-methylome omnibus (CMO) test and leveraged data from the COVID-19 Host Genetics Initiative (HGI) comparing 9,986 hospitalized COVID-19 patients and 1,877,672 population controls. Second, we evaluated associations using the complementary S-PrediXcan method and leveraging blood and lung tissue gene expression prediction models. Third, we assessed associations of the identified genes with another COVID-19 phenotype, comparing very severe respiratory confirmed COVID versus population controls. Finally, we applied a fine-mapping method, fine-mapping of gene sets (FOGS), to prioritize putative causal genes.
Through analyses of the COVID-19 HGI using complementary CMO and S-PrediXcan methods along with fine-mapping, XCR1, CCR2, SACM1L, OAS3, NSF, WNT3, NAPSA, and IFNAR2 are identified as putative causal genes for COVID-19 severity.
We identified eight genes at five genomic loci as putative causal genes for COVID-19 severity.
确定严重急性呼吸综合征冠状病毒 2 的可能因果靶标至关重要，这可能有助于选择药物重新利用的方案，以减轻 COVID-19 对公众健康的负担。
我们应用互补的方法和多阶段设计来确定 COVID-19 严重程度的最可能因果基因。首先，我们应用跨甲基组整体（CMO）检验，并利用 COVID-19 宿主遗传学倡议（HGI）的数据，比较了 9986 名住院 COVID-19 患者和 1877672 名人群对照。其次，我们使用互补的 S-PrediXcan 方法评估关联，并利用血液和肺组织基因表达预测模型。第三，我们评估了鉴定基因与另一个 COVID-19 表型的关联，将非常严重的呼吸道确诊 COVID 与人群对照进行比较。最后，我们应用精细映射方法，即基因集精细映射（FOGS），对可能的因果基因进行优先级排序。
通过使用互补的 CMO 和 S-PrediXcan 方法以及精细映射对 COVID-19 HGI 进行分析，确定了 XCR1、CCR2、SACM1L、OAS3、NSF、WNT3、NAPSA 和 IFNAR2 作为 COVID-19 严重程度的可能因果基因。
我们在五个基因组位点确定了八个基因作为 COVID-19 严重程度的可能因果基因。
