Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; Nuffield Department of Women's and Reproduction Health, Oxford University, Oxford, United Kingdom.
Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates.
EBioMedicine. 2021 Dec;74:103695. doi: 10.1016/j.ebiom.2021.103695. Epub 2021 Nov 11.
The heterogeneity in symptomatology and phenotypic profile attributable to COVID-19 is widely unknown. The objective of this manuscript is to conduct a trans-ancestry genome wide association study (GWAS) meta-analysis of COVID-19 severity to improve the understanding of potentially causal targets for SARS-CoV-2.
This cross-sectional study recruited 646 participants in the UAE that were divided into two phenotypic groups based on the severity of COVID-19 phenotypes, hospitalized (n=482) and non-hospitalized (n=164) participants. Hospitalized participants were COVID-19 patients that developed acute respiratory distress syndrome (ARDS), pneumonia or progression to respiratory failure that required supplemental oxygen therapy or mechanical ventilation support or had severe complications such as septic shock or multi-organ failure. We conducted a trans-ancestry meta-analysis GWAS of European (n=302), American (n=102), South Asian (n=99), and East Asian (n=107) ancestry populations. We also carried out comprehensive post-GWAS analysis, including enrichment of SNP associations in tissues and cell-types, expression quantitative trait loci and differential expression analysis.
Eight genes demonstrated a strong association signal: VWA8 gene in locus 13p14·11 (SNP rs10507497; p=9·54 x10), PDE8B gene in locus 5q13·3 (SNP rs7715119; p=2·19 x10), CTSC gene in locus 11q14·2 (rs72953026; p=2·38 x10), THSD7B gene in locus 2q22·1 (rs7605851; p=3·07x10), STK39 gene in locus 2q24·3 (rs7595310; p=4·55 x10), FBXO34 gene in locus 14q22·3 (rs10140801; p=8·26 x10), RPL6P27 gene in locus 18p11·31 (rs11659676; p=8·88 x10), and METTL21C gene in locus 13q33·1 (rs599976; p=8·95 x10). The genes are expressed in the lung, associated to tumour progression, emphysema, airway obstruction, and surface tension within the lung, as well as an association to T-cell-mediated inflammation and the production of inflammatory cytokines.
We have discovered eight highly plausible genetic association with hospitalized cases in COVID-19. Further studies must be conducted on worldwide population genetics to facilitate the development of population specific therapeutics to mitigate this worldwide challenge.
This review was commissioned as part of a project to study the host cell receptors of coronaviruses funded by Khalifa University's CPRA grant (Reference number 2020-004).
COVID-19 的症状和表型谱的异质性尚不清楚。本文的目的是对 COVID-19 严重程度进行跨种族全基因组关联研究（GWAS）荟萃分析，以提高对 SARS-CoV-2 潜在因果靶点的理解。
本横断面研究招募了在阿联酋的 646 名参与者，根据 COVID-19 表型的严重程度将其分为两组：住院（n=482）和非住院（n=164）参与者。住院患者是指患有急性呼吸窘迫综合征（ARDS）、肺炎或进展为需要补充氧气治疗或机械通气支持的呼吸衰竭、或患有败血症性休克或多器官衰竭等严重并发症的 COVID-19 患者。我们对欧洲（n=302）、美洲（n=102）、南亚（n=99）和东亚（n=107）血统人群进行了跨种族荟萃分析 GWAS。我们还进行了全面的 GWAS 后分析，包括 SNP 关联在组织和细胞类型中的富集、表达数量性状基因座和差异表达分析。
有八个基因显示出强烈的关联信号：13p14.11 位置的 VWA8 基因（SNP rs10507497；p=9.54 x10）、5q13.3 位置的 PDE8B 基因（SNP rs7715119；p=2.19 x10）、11q14.2 位置的 CTSC 基因（rs72953026；p=2.38 x10）、2q22.1 位置的 THSD7B 基因（rs7605851；p=3.07x10）、2q24.3 位置的 STK39 基因（rs7595310；p=4.55 x10）、14q22.3 位置的 FBXO34 基因（rs10140801；p=8.26 x10）、18p11.31 位置的 RPL6P27 基因（rs11659676；p=8.88 x10）和 13q33.1 位置的 METTL21C 基因（rs599976；p=8.95 x10）。这些基因在肺中表达，与肿瘤进展、肺气肿、气道阻塞和肺表面张力有关，也与 T 细胞介导的炎症和炎症细胞因子的产生有关。
我们发现了与 COVID-19 住院病例有高度关联的八个基因。必须在全球人群遗传学中进行进一步的研究，以促进针对这一全球挑战的人群特异性治疗方法的开发。
本综述是作为研究冠状病毒宿主细胞受体项目的一部分而委托撰写的，该项目由 Khalifa 大学的 CPRA 资助（参考号 2020-004）。
