Analysis of genome risks variations associated with severe Covid-19 across the worldwide populations
Epidemiological observations indicate that disease severity and mortality from COVID-19 vary between countries. In addition to socioeconomic and climatic factors, the underlying causes may also be in genetics. The study conducted by researchers of FSBI RCMG, Institute of General Genetics RAS and Russian Medical Academy of Continuing Professional Education, the frequencies of genetic markers rs11385942 and rs657152, which, according to the literature, are associated with a more severe course of COVID-19, were studied in populations of Russia and the world. O.P. Balanovsky, Doctor of biological science, Chief researcher of the FSBI RCMG Human Population Genetics Laboratory, Professor of RAS was the first author of the article. The researchers genotyped 1883 samples from 91 populations from Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Lithuania, Mongolia, Russia, Tajikistan, Ukraine, and Uzbekistan. In addition, they used a global database of different regions; the combined database included 60 populations.
The first marker (rs11385942) has the highest frequency (20-30%) in South Asian populations, followed by Middle Eastern and European populations (5-15%). It is very rare or absent in East Asia, Siberia, American Indians, and sub-Saharan African populations. They performed a more detailed analysis in populations of Russia and neighboring countries. The map shows that in the direction from west to east the frequency of this marker gradually decreases from 13-16% in Ukraine, Belarus and westernmost Russian populations to the 0% frequency in Kamchatka and Chukotka. On average, its frequency in populations of European Russia is 11%, in Siberia 3%, and in most countries of Central Asia 1-4%.
The frequency of another genetic variant (rs657152) is more evenly distributed throughout the world and is generally rather high in the countries of the Old World. Its maximum frequency (over 50%) is observed in sub-Saharan Africa; in the majority of Eurasian populations, it ranges from 40% to 50%. It is almost absent in American Indians and Australian aborigines.
The rs657152 variation on 9 chromosome is associated with AB0 blood group. As previously shown, people with A blood group have a slightly higher risk of respiratory failure than people with 0 blood group. The distribution map of the "risky" A(II) blood group shows that its high frequencies (30% and higher) are found in Western Europe, somewhat lower in the Volga-Ural region of Eastern Europe and even lower (10-20%) in Siberia, East Asia and Sub-Saharan Africa. In most populations of South Asia, the frequency of A (II) group is medium (15-20%).
When comparing the official statistics on COVID-19 with the frequency of the studied markers, a significant positive correlation (0.63) was found between the frequency of the rs657152 in Russian populations and the mortality rate; the correlation did not reach the level of reliability for the frequency of the other marker. No correlations were found on a global scale, which may be related to differences in case registration in different countries.
Based on the results of this study, the authors concluded that genetic variation between populations makes small but real contribution into the heterogeneity of the COVID-19 pandemic worldwide.
Balanovsky О., Petrushenko V., Mirzaev K., Abdullaev S., Gorin I., Chernevskiy D., Agdzhoyan A., Balanovska E., Sychev D. The variation of genome sites associated with severe COVID-19 across populations the worldwide and national patterns.
www.medrxiv.org/content/10.1101/2020.11.22.20236414v1