Investigating the likely association between genetic ancestry and COVID-19 manifestations

BackgroundThe novel coronavirus: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world leading to catastrophic consequences. However, SARS-CoV-2 infection has shown discernible variability across the globe. While in some countries people are recovering relatively quickly, in others, recovery times have been comparatively longer and number of individuals succumbing to it are high. This variability in coronavirus disease 2019 (COVID-19) susceptibility is suggestive of a likely association between the genetic-make up of affected individuals modulated by their ancestry and the severity of COVID-19 manifestations. ObjectiveIn this study, we aimed to evaluate the potential association between an individuals genetic ancestry and the extent of COVID-19 disease presentation employing Europeans as the case study. In addition, using a genome wide association (GWAS) approach we sought to discern the putative single nucleotide polymorphism (SNP) markers and genes that may be likely associated with differential COVID-19 manifestations by comparative analyses of the European and East Asian genomes. MethodTo this end, we employed 10,215 ancient and modern genomes across the globe assessing 597,573 SNPs obtained from the databank of Dr. David Reich, Harvard Medical School, USA to evaluate the likely correlation between European ancestry and COVID-19 manifestations. Ancestry proportions were determined using qpAdm program implemented in AdmixTools v5.1. Pearsons correlation coefficient (r) between various ancestry proportions of European genomes and COVID-19 death/recovery ratio was calculated and its significance was statistically evaluated. Genome wide association study (GWAS) was performed in PLINK v1.9 to investigate SNPs with significant allele frequency variations among European and East Asian genomes that likely correlated with differential COVID-19 infectivity. ResultsWe found significant positive correlation (r=0.58, P=0.03) between West European hunter gatherers (WHG) ancestral fractions and COVID-19 death/recovery ratio for data as of 5th April 2020. This association discernibly amplified (r=0.77, P=0.009) upon reanalyses based on data as of 30th June 2020, removing countries with small sample sizes and adding those that are a bridge between Europe and Asia. Using GWAS we further identified 404 immune response related SNPs by comparing publicly available 753 genomes from various European countries against 838 genomes from various Eastern Asian countries. Prominently, we identified that SNPs associated with immune-system related pathways such as interferon stimulated antiviral response, adaptive and innate immune system and IL-6 dependent immune responses show significant differences in allele frequencies [Chi square values ([≥]1500; P{approx}0)] between Europeans and East Asians. ConclusionSo far, to the best of our knowledge, this is the first study investigating the likely association between host genetic ancestry and COVID-19 severity. These findings improve our overall understanding of the putative genetic modifiers of COVID-19 clinical presentation. We note that the development of effective therapeutics will benefit immensely from more detailed analyses of individual genomic sequence data from COVID-19 patients of varied ancestries.