[en] The course of COVID-19 is highly variable, with genetics playing a significant role. Through large-scale genetic association studies, a link between single nucleotide polymorphisms and disease susceptibility and severity was established. However, individual single nucleotide polymorphisms identified thus far have shown modest effects, indicating a polygenic nature of this trait, and individually have limited predictive performance. To address this limitation, we investigated the performance of a polygenic risk score model in the context of COVID-19 severity in a Russian population. A genome-wide polygenic risk score model including information from over a million common single nucleotide polymorphisms was developed using summary statistics from the COVID-19 Host Genetics Initiative consortium. Low-coverage sequencing (5x) was performed for ~1000 participants, and polygenic risk score values were calculated for each individual. A multivariate logistic regression model was used to analyse the association between polygenic risk score and COVID-19 outcomes. We found that individuals in the top 10% of the polygenic risk score distribution had a markedly elevated risk of severe COVID-19, with adjusted odds ratio of 2.9 (95% confidence interval: 1.8-4.6, p-value = 4e-06), and more than four times higher risk of mortality from COVID-19 (adjusted odds ratio = 4.3, p-value = 2e-05). This study highlights the potential of polygenic risk score as a valuable tool for identifying individuals at increased risk of severe COVID-19 based on their genetic profile.
Disciplines :
Genetics & genetic processes
Author, co-author :
Nostaeva, Arina ; Université de Liège - ULiège > Département de gestion vétérinaire des Ressources Animales (DRA) > Génomique animale ; City Hospital No. 40 of Kurortny District, St. Petersburg State Budgetary Healthcare Institution, Sestroretsk, Russia ; St. Petersburg State University, St. Petersburg, Russia
Shimansky, Valentin; City Hospital No. 40 of Kurortny District, St. Petersburg State Budgetary Healthcare Institution, Sestroretsk, Russia ; St. Petersburg State University, St. Petersburg, Russia
Apalko, Svetlana; City Hospital No. 40 of Kurortny District, St. Petersburg State Budgetary Healthcare Institution, Sestroretsk, Russia ; St. Petersburg State University, St. Petersburg, Russia
Kuznetsov, Ivan; Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russia
Sushentseva, Natalya; City Hospital No. 40 of Kurortny District, St. Petersburg State Budgetary Healthcare Institution, Sestroretsk, Russia
Popov, Oleg; City Hospital No. 40 of Kurortny District, St. Petersburg State Budgetary Healthcare Institution, Sestroretsk, Russia ; St. Petersburg State University, St. Petersburg, Russia
Asinovskaya, Anna; City Hospital No. 40 of Kurortny District, St. Petersburg State Budgetary Healthcare Institution, Sestroretsk, Russia ; St. Petersburg State University, St. Petersburg, Russia
Mosenko, Sergei; City Hospital No. 40 of Kurortny District, St. Petersburg State Budgetary Healthcare Institution, Sestroretsk, Russia ; St. Petersburg State University, St. Petersburg, Russia
Karssen, Lennart; PolyKnomics BV, s-Hertogenbosch, The Netherlands
Sarana, Andrey; St. Petersburg State University, St. Petersburg, Russia
Aulchenko, Yurii; PolyKnomics BV, s-Hertogenbosch, The Netherlands
Shcherbak, Sergey; City Hospital No. 40 of Kurortny District, St. Petersburg State Budgetary Healthcare Institution, Sestroretsk, Russia ; St. Petersburg State University, St. Petersburg, Russia
Language :
English
Title :
Case-control association study between polygenic risk score and COVID-19 severity in a Russian population using low-pass genome sequencing.
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