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

Abstract

The novel coronavirus 2019-nCoV/SARS-CoV-2 infection has shown discernible variability across the globe. While in some countries people are recovering relatively quicker, in others, recovery times have been comparatively longer and numbers of those succumbing to it high.In this study, we aimed to evaluate the likely association between an individual's ancestry and the extent of COVID-19 manifestation employing Europeans as the case study. We employed 10,215 ancient and modern genomes across the globe assessing 597,573 single nucleotide polymorphisms (SNPs). Pearson's correlation coefficient (r) between various ancestry proportions of European genomes and COVID-19 death/recovery ratio was calculated and its significance was statistically evaluated. We found significant positive correlation (p=0.03) between European Mesolithic hunter gatherers (WHG) ancestral fractions and COVID-19 death/recovery ratio and a marginally significant negative correlation (p=0.06) between Neolithic Iranian ancestry fractions and COVID-19 death/recovery ratio. We further identified 404 immune response related single nucleotide polymorphisms (SNPs) by comparing publicly available 753 genomes from various European countries against 838 genomes from various Eastern Asian countries in a genome wide association study (GWAS). Prominently, we identified that SNPs associated with Interferon stimulated antiviral response, Interferon-stimulated gene 15 mediated antiviral mechanism and 2′-5′ oligoadenylate synthase mediated antiviral response show large differences in allele frequencies between Europeans and East Asians. Overall, to the best of our knowledge, this is the first study evaluating the likely association between genetic ancestry and COVID-19 manifestation. While our current findings improve our overall understanding of the COVID-19, 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.

Geographic components of SARS-CoV-2 expansion: a hypothesis

“…Lower transmission rates and reduced severity of COVID-19 infections were initially noted on the Qinghai-Tibetan plateau during the virus's rapid spread across Asia (49,85). Growing evidence in support of similar trends have now been shown in Bolivia (1); Peru, Argentina, and Chile (24); HA regions of central Ecuador (1,63); remote villages in Papua (78); the Sichuan province of mainland China (46,91); Nepal and Bhutan (3); and Himalayan regions of India including Arunachal Pradesh and Ladakh (24). While it is acknowledged the pandemic is still in its early stages in some of these regions, the disproportionate spread of SARS-CoV-2 deserves further attention.…”

“…Genomic ancestry supports genetic links between the anti-COVID-19 display among HA populations. In HA regions such as Ladakh, Arunachal Pradesh, Manipur, and Mizoram, the Tibeto-Burman genetic composition predominates and COVID-19 infections have been limited (24). Similarly, higher fractions of Paleo-Eskimo ancestry in HA regions of Peru and Mexico have been accompanied by considerably lower death rates (24).…”

Ethnicity-dependent allele frequencies are correlated with COVID-19 case fatality rate

“…To understand the genetic background of complex phenotypes in human populations, researchers commonly assess correlations with allele frequency (AF) 16,17 . This approach has identi ed a correlation between ancestral genetic composition and the CFR of COVID-19 17 . However, few have examined speci c variants, their frequencies and individual contributions to SARS-CoV-2 susceptibility.…”

Ethnicity-dependent allele frequencies are correlated with COVID-19 case fatality rate

“…To understand the genetic background of complex phenotypes in human populations, researchers commonly assess correlations with allele frequency (AF) 16,17 . This approach has identi ed a correlation between ancestral genetic composition and the CFR of COVID-19 17 . However, few have examined speci c variants, their frequencies and individual contributions to SARS-CoV-2 susceptibility.…”

“…However, few have examined speci c variants, their frequencies and individual contributions to SARS-CoV-2 susceptibility. Some reports are also based only on low-resolution intercontinental comparisons between Europeans and East Asians [16][17][18] . Moreover, we know little about the evolutionary history of SARS-CoV-2 susceptibilityassociated variants, including when they occurred or how their frequencies might have changed over time.…”