The lack of information about the frequency of pharmacogenetic markers in Russia impedes the adoption of personalized treatment algorithms originally developed for West European populations. The aim of this paper was to study the distribution of some clinically significant pharmacogenetic markers across Russia. A total of 45 pharmacogenetic markers were selected from a few population genetic datasets, including ADME, drug target and hemostasis-controlling genes. The total number of donors genotyped for these markers was 2,197. The frequencies of these markers were determined for 50 different populations, comprised of 137 ethnic and subethnic groups. A comprehensive pharmacogenetic atlas was created, i.e. a systematic collection of gene geographic maps of frequency variation for 45 pharmacogenetic DNA markers in Russia and its neighbor states. The maps revealed 3 patterns of geographic variation. Clinal variation (a gradient change in frequency along the East-West axis) is observed in the pharmacogenetic markers that follow the main pattern of variation for North Eurasia (13% of the maps). Uniform distribution singles out a group of markers that occur at average frequency in most Russian regions (27% of the maps). Focal variation is observed in the markers that are specific to a certain group of populations and are absent in other regions (60% of the maps). The atlas reveals that the average frequency of the marker and its frequency in individual populations do not indicate the type of its distribution in Russia: a gene geographic map is needed to uncover the pattern of its variation.

SUMMARYBackgroundThe knowledge of clinically relevant markers distribution might become a useful tool in COVID-19 therapy using personalized approach in the lack of unified recommendations for COVID-19 patients management during pandemic. We aimed to identify the frequencies and distribution patterns of rs11385942 and rs657152 polymorphic markers, associated with severe COVID-19, among populations of the world, as well at the national level within Russia. The study was also dedicated to reveal whether population frequencies of both polymorphic markers are associated with COVID-19 cases, recovery and death rates.MethodsWe genotyped 1883 samples from 91 ethnic populations from Russia and neighboring countries by rs11385942 and rs657152 markers. Local populations which were geographically close and genetically similar were pooled into 28 larger groups. In the similar way we compiled a dataset on the other regions of the globe using genotypes extracted or imputed from the available datasets (32 populations worldwide). The differences in alleles frequencies between groups were estimated and the frequency distribution geographic maps have been constructed. We run the correlation analysis of both markers frequencies in various populations with the COVID-19 epidemiological data on the same populations.FindingsThe cartographic analysis revealed that distribution of rs11385942 follows the West Eurasian pattern: it is frequent in Europeans, West Asians, and particularly in South Asians but rare or absent in all other parts of the globe. Notably, there is no abrupt changes in frequency across Eurasia but the clinal variation instead. The distribution of rs657152 is more homogeneous. Higher population frequencies of both risk alleles correlated positively with the death rate. For the rs11385942 we can state the tendency only (r=0,13, p=0.65), while for rs657152 the correlation was significantly high (r=0,59, p=0,02). These reasonable correlations were obtained on the Russian dataset, but not on the world dataset.InterpretationUsing epidemiological statistics on Russia and neighboring countries we revealed the evident correlation of the risk alleles frequencies with the death rate from COVID-19. The lack of such correlations at the world level should be attributed to the differences in the ways epidemiological data have been counted in different countries. So that, we believe that genetic differences between populations make small but real contribution into the heterogeneity of the pandemic worldwide. New studies on the correlations between COVID-19 recovery/mortality rates and population’s gene pool are urgently needed.

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The correlation between the risk of death from COVID-19 and the patient's ethnogeographic origin has been previously detected. LZTFL1 gene was identified as a potential marker of a two times higher risk of severe COVID-19. The study was aimed to assess spatial variation in the LZTFL1 SNP markers in indigenous populations of Russia and the world. Spatial variation in the LZTFL1 polymorphic markers was analyzed in 28 metapopulations (97 ethnic groups) of North Eurasia (n = 1980) and 34 world's metapopulations (n = 3637) by bioinformatics, statistical and cartographic methods. In North Eurasia, the major geographic variation vectors, North–South and West–East, are generally in line with the Caucasoid–Mongoloid anthropological vector. Global variation also corresponds to anthropological features: each cluster of indigenous populations includes only those from the place where it originates: Africa, Asia, or America. Indo-European cluster integrates Caucasoid populations of Europe and Asia. All four clusters of the world's indigenous population are separated from each other. The huge genetic diversity of Russia peoples and neighboring countries forms a bridge between three continents: Europe, Asia and America. Cartographic atlas for spatial variation in 11 LZTFL1 markers in the populations has been created. The following major patterns have been revealed: а) the world's extrema fall on the indigenous populations of Africa and America; 2) Eurasia constitutes a transition zone between these two extrema, but has its own patterns and shows enormous scale of variation shows enormous variation on a global scale; 3) the genetic landscape of Russia tends to be seamlessly integrated into the Eurasian landscape.