AUTHOR=Smatti Maria K. , Al-Sarraj Yasser A. , Albagha Omar , Yassine Hadi M. 

TITLE=Host Genetic Variants Potentially Associated With SARS-CoV-2: A Multi-Population Analysis

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.578523

DOI=10.3389/fgene.2020.578523

ISSN=1664-8021

ABSTRACT=<sec><title>Background</title><p>Clinical outcomes of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) showed enormous inter-individual and inter-population differences, possibly due to host genetics differences. Earlier studies identified single nucleotide polymorphisms (SNPs) associated with SARS-CoV-1 in Eastern Asian (EAS) populations. In this report, we aimed at exploring the frequency of a set of genetic polymorphisms that could affect SARS-CoV-2 susceptibility or severity, including those that were previously associated with SARS-CoV-1.</p></sec><sec><title>Methods</title><p>We extracted the list of SNPs that could potentially modulate SARS-CoV-2 from the genome wide association studies (GWAS) on SARS-CoV-1 and other viruses. We also collected the expression data of these SNPs from the expression quantitative trait loci (eQTLs) databases. Sequences from Qatar Genome Programme (QGP, <italic>n</italic> = 6,054) and 1000Genome project were used to calculate and compare allelic frequencies (AF).</p></sec><sec><title>Results</title><p>A total of 74 SNPs, located in 10 genes: <italic>ICAM3</italic>, <italic>IFN</italic>-γ, <italic>CCL2</italic>, <italic>CCL5</italic>, <italic>AHSG, MBL</italic>, <italic>Furin</italic>, <italic>TMPRSS2</italic>, <italic>IL4</italic>, and <italic>CD209</italic> promoter, were identified. Analysis of Qatari genomes revealed significantly lower AF of risk variants linked to SARS-CoV-1 severity (<italic>CCL2</italic>, <italic>MBL</italic>, <italic>CCL5</italic>, <italic>AHSG</italic>, and <italic>IL4</italic>) compared to that of 1000Genome and/or the EAS population (up to 25-fold change). Conversely, SNPs in <italic>TMPRSS2</italic>, <italic>IFN</italic>-γ, <italic>ICAM3</italic>, and <italic>Furin</italic> were more common among Qataris (average 2-fold change). Inter-population analysis showed that the distribution of risk alleles among Europeans differs substantially from Africans and EASs. Remarkably, Africans seem to carry extremely lower frequencies of SARS-CoV-1 susceptibility alleles, reaching to 32-fold decrease compared to other populations.</p></sec><sec><title>Conclusion</title><p>Multiple genetic variants, which could potentially modulate SARS-CoV-2 infection, are significantly variable between populations, with the lowest frequency observed among Africans. Our results highlight the importance of exploring population genetics to understand and predict COVID-19 outcomes. Indeed, further studies are needed to validate these findings as well as to identify new genetic determinants linked to SARS-CoV-2.</p></sec>