Variation of Genomic Sites Associated with Severe Covid-19 Across Populations: Global and National Patterns

Abstract

Background: Information about the distribution of clinically significant genetic markers in different populations may be helpful in elaborating personalized approaches to the clinical management of COVID-19 in the absence of consensus guidelines.

Aim: Analyze frequencies and distribution patterns of two markers associated with severe COVID-19 (rs11385942 and rs657152) and look for potential correlations between these markers and deaths from COVID-19 among populations in Russia and across the world.

Methods: We genotyped 1883 samples from 91 ethnic groups pooled into 28 populations representing Russia and its neighbor states. We also compiled a dataset on 32 populations from other regions using genotypes extracted or imputed from the available databases. Geographic maps showing the frequency distribution of the analyzed markers were constructed using the obtained data.

Results: The cartographic analysis revealed that rs11385942 distribution follows the West Eurasian pattern: the marker is frequent among the populations of Europe, West Asia and South Asia but rare or absent in all other parts of the globe. Notably, the transition from high to low rs11385942 frequencies across Eurasia is not abrupt but follows the clinal variation pattern instead. The distribution of rs657152 is more homogeneous. The analysis of correlations between the frequencies of the studied markers and the epidemiological characteristics of COVID-19 in a population revealed that higher frequencies of both risk alleles correlated positively with mortality from this disease. For rs657152, the correlation was especially strong (r = 0.59, p = 0.02). These reasonable correlations were observed for the "Russian" dataset only: no such correlations were established for the "world" dataset. This could be attributed to the differences in methodology used to collect COVID-19 statistics in different countries.

Conclusion: Our findings suggest that genetic differences between populations make a small yet tangible contribution to the heterogeneity of the pandemic worldwide.

Keywords: AB0; gene geography; genetic markers; rs11385942; rs657152; severe COVID-19.

Figure 1

The studied populations. Blue squares show locations of population samples genotyped specifically for this study (the Russian dataset). Green diamonds show locations of population samples described in other sources and reanalyzed in the course of this study (the world dataset).

Figure 2

Global variation of rs11385942_GA frequencies. Four colors mark areas of 4 frequency ranges of this risk allele. The black points represent the populations analyzed. Abbreviations in the statistical legend indicate the following.

Figure 3

Variation of rs11385942_GA frequencies across Russia and its neighbor states. The frequency spectrum here is more detailed than the one shown on the world map (Figure 2). The black points represent the populations analyzed. Abbreviations in the statistical legend indicate the following.

Figure 4

Global variation of rs657152_A frequencies. Four colors mark areas with four intervals of frequencies of this risk allele, according to the scale. The black points represent the populations analyzed. Abbreviations in the statistical legend indicate the following.

Figure 5

Distribution frequencies of blood group A (the ABO system) in the world. The map was modified from previous study. The black points represent the populations analyzed. Abbreviations in the statistical legend indicate the following.