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ORIGINAL RESEARCH article

Front. Med.
Sec. Infectious Diseases: Pathogenesis and Therapy
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1409714

GWAS and polygenic risk score of severe COVID-19 in Eastern Europe

Provisionally accepted
Elena Kovalenko Elena Kovalenko 1Layal Shaheen Layal Shaheen 1Ekaterina Vergasova Ekaterina Vergasova 1Alexey Kamelin Alexey Kamelin 1Valerya Rubinova Valerya Rubinova 1Dmitry Kharitonov Dmitry Kharitonov 1Anna Kim Anna Kim 1Nikolay Plotnikov Nikolay Plotnikov 1Artem Elmuratov Artem Elmuratov 1Natalia Borovkova Natalia Borovkova 2Maya Storozheva Maya Storozheva 2Sergey Solonin Sergey Solonin 2Irina Gilyazova Irina Gilyazova 3,4Petr Mironov Petr Mironov 4Elza Khusnutdinova Elza Khusnutdinova 3,4Sergey Petrikov Sergey Petrikov 2Anna Ilinskaya Anna Ilinskaya 5Valery Ilinsky Valery Ilinsky 5Alexander Rakitko Alexander Rakitko 1*
  • 1 Genotek Ltd., Moscow, Russia
  • 2 Institute of Clinical Medicine. N.V. Sklifosovsky, I.M. Sechenov First Moscow State Medical University, Moscow, Moscow Oblast, Russia
  • 3 Institute of Biochemistry and Genetics of Ufa Scientific Centre (RAS), Ufa, Russia
  • 4 Bashkir State Medical University, Ufa, Bashkortostan, Russia
  • 5 Eligens SIA, Mārupe, Latvia

The final, formatted version of the article will be published soon.

    Background: COVID-19 disease has been confirmed more than 772 million times and almost 7 million people have died so far. The severe course of COVID-19 is thought to be preventable with appropriate treatment, but thorough research of the genetic nature of the COVID-19 pathogenesis is needed for its effectiveness. Methods: We performed a genome-wide association study (GWAS) on 7124 people (6400 controls, who had survived COVID-19 without a severe course; 724 cases -patients with severe COVID-19). The inclusion criteria were ARDS (acute respiratory distress syndrome), ARF (acute respiratory failure) requiring respiratory support or CT scans typical of severe COVID-19 infection without any competing diseases. We also trained a polygenic risk score (PRS) model to detect individuals in high-risk group. Results: We identified 2 genome-wide significant loci (p-value <5x10 -8 ) and one locus with approximately genome-wide significance (p-value = 5.92x10 -8 -6.15x10 -8 ). The most genome-wide significant variants were located in the LZTFL1 gene, which was mentioned in several previous GWAS studies. Our PRS model results indicated that people who are in a top-10% group of PRS had twice higher risk of severe course of the disease than those who have median risk (odds ratio, OR = 2.18 [1.66, 2.86], p-value = 8.9x10 -9 ).Conclusions: We performed one of the largest studies of genetics of severe course of COVID-19 on the Eastern European cohort to date. Our results are in concordance with previous research and will guide further epidemiologic studies on host genetics as well as on the development of appropriate treatment.

    Keywords: COVID-19, GWAS, Polygenic risk score, Severe COVID-19, LZTFL1 gene

    Received: 30 Mar 2024; Accepted: 30 Jul 2024.

    Copyright: © 2024 Kovalenko, Shaheen, Vergasova, Kamelin, Rubinova, Kharitonov, Kim, Plotnikov, Elmuratov, Borovkova, Storozheva, Solonin, Gilyazova, Mironov, Khusnutdinova, Petrikov, Ilinskaya, Ilinsky and Rakitko. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Alexander Rakitko, Genotek Ltd., Moscow, Russia

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.