Genome-wide association study of hospitalized COVID-19 patients in the United Arab Emirates

Background: 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. Methods: 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. Findings: Eight genes demonstrated a strong association signal: VWA8 gene in locus 13p14·11 (SNP rs10507497; p=9·54 x10^-7), PDE8B gene in locus 5q13·3 (SNP rs7715119; p=2·19 x10^-6), CTSC gene in locus 11q14·2 (rs72953026; p=2·38 x10^-6), THSD7B gene in locus 2q22·1 (rs7605851; p=3·07x10^-6), STK39 gene in locus 2q24·3 (rs7595310; p=4·55 x10^-6), FBXO34 gene in locus 14q22·3 (rs10140801; p=8·26 x10^-6), RPL6P27 gene in locus 18p11·31 (rs11659676; p=8·88 x10^-6), and METTL21C gene in locus 13q33·1 (rs599976; p=8·95 x10^-6). 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. Interpretation: 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. Funding: 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).