Abstract
BackgroundClinical 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.MethodsWe 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, n = 6,054) and 1000Genome project were used to calculate and compare allelic frequencies (AF).ResultsA total of 74 SNPs, located in 10 genes: ICAM3, IFN-γ, CCL2, CCL5, AHSG, MBL, Furin, TMPRSS2, IL4, and CD209 promoter, were identified. Analysis of Qatari genomes revealed significantly lower AF of risk variants linked to SARS-CoV-1 severity (CCL2, MBL, CCL5, AHSG, and IL4) compared to that of 1000Genome and/or the EAS population (up to 25-fold change). Conversely, SNPs in TMPRSS2, IFN-γ, ICAM3, and Furin 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.ConclusionMultiple 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.
Highlights
Viruses have been replicating in vertebrates for more than 450 million years (Aiewsakun and Katzourakis, 2017)
These single nucleotide polymorphisms (SNPs) are located in 10 genes: intercellular adhesion molecule-3 (ICAM3), IFN-γ, CCL2, CCL5, AHSG, Mannose-binding lectin (MBL), Furin, TMPRSS2, interleukin 4 (IL4), and CD209 promoter
We calculated the fold difference in the Allele frequencies (AF) in comparison to the Eastern Asian (EAS) population (n = 504), since all these susceptibility SNPs were originally identified in the Chinese population (Figure 1)
Summary
Viruses have been replicating in vertebrates for more than 450 million years (Aiewsakun and Katzourakis, 2017) This host-pathogen interaction has exerted a selective pressure over time and affected specific allelic frequencies of certain populations to favor a particular genetic variant. The frequent outbreaks of coronaviruses in China (SARSCoV-1 in 2003, and the current SARS-CoV-2) raised the possibility that Asians have unique genetic factors that influence their susceptibility to coronaviruses (Chen et al, 2020). 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. We aimed at exploring the frequency of a set of genetic polymorphisms that could affect SARSCoV-2 susceptibility or severity, including those that were previously associated with SARS-CoV-1
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