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

• Published in: Frontiers in medicine Vol. 11; p. 1409714
• Main Authors: Kovalenko, Elena, Shaheen, Layal, Vergasova, Ekaterina, Kamelin, Alexey, Rubinova, Valerya, Kharitonov, Dmitry, Kim, Anna, Plotnikov, Nikolay, Elmuratov, Artem, Borovkova, Natalia, Storozheva, Maya, Solonin, Sergey, Gilyazova, Irina, Mironov, Petr, Khusnutdinova, Elza, Petrikov, Sergey, Ilinskaya, Anna, Ilinsky, Valery, Rakitko, Alexander
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 19-09-2024
• Subjects: COVID-19; GWAS; LZTFL1 gene; Medicine; polygenic risk score; severe COVID-19; COVID-19; GWAS; polygenic risk score; LZTFL1 gene; severe COVID-19
• ISSN: 2296-858X; 2296-858X
• DOI: 10.3389/fmed.2024.1409714

COVID-19 disease has infected more than 772 million people, leading to 7 million deaths. Although the severe course of COVID-19 can be prevented using appropriate treatments, effective interventions require a thorough research of the genetic factors involved in its pathogenesis.
We conducted a genome-wide association study (GWAS) on 7,124 individuals (comprising 6,400 controls who had mild to moderate COVID-19 and 724 cases with severe COVID-19). The inclusion criteria were acute respiratory distress syndrome (ARDS), acute respiratory failure (ARF) requiring respiratory support, or CT scans indicative of severe COVID-19 infection without any competing diseases. We also developed a polygenic risk score (PRS) model to identify individuals at high risk.
We identified two genome-wide significant loci (
-value <5 × 10
) and one locus with approximately genome-wide significance (
-value = 5.92 × 10
-6.15 × 10
). The most genome-wide significant variants were located in the
(
) gene, which has been highlighted in several previous GWAS studies. Our PRS model results indicated that individuals in the top 10% group of the PRS had twice the risk of severe course of the disease compared to those at median risk [odds ratio = 2.18 (1.66, 2.86),
-value = 8.9 × 10
].
We conducted one of the largest studies to date on the genetics of severe COVID-19 in an Eastern European cohort. Our results are consistent with previous research and will guide further epidemiologic studies on host genetics, as well as for the development of targeted treatments.