TY - JOUR

T1 - Case-control association study between polygenic risk score and COVID-19 severity in a Russian population using low-pass genome sequencing

AU - Nostaeva, A.

AU - Shimansky, V.

AU - Apalko, S.

AU - Kuznetsov, I.

AU - Sushentseva, N.

AU - Popov, O.

AU - Asinovskaya, A.

AU - Mosenko, S.

AU - Karssen, L.

AU - Sarana, A.

AU - Aulchenko, Y.

AU - Shcherbak, S.

N1 - Export Date: 01 November 2025; Cited By: 0; Correspondence Address: A. Nostaeva; City Hospital No. 40 of Kurortny District, St. Petersburg State Budgetary Healthcare Institution, Sestroretsk, Russian Federation; email: avnostaeva@gmail.com; CODEN: EPINE

PY - 2024

Y1 - 2024

N2 - 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. © 2025 Elsevier B.V., All rights reserved.

AB - 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. © 2025 Elsevier B.V., All rights reserved.

KW - COVID-19

KW - genetic predisposition

KW - genome-wide association studies

KW - low-pass whole genome sequencing

KW - polygenic risk score

KW - acute respiratory distress syndrome

KW - adult

KW - Article

KW - case control study

KW - chronic obstructive lung disease

KW - computer assisted tomography

KW - controlled study

KW - coronavirus disease 2019

KW - diagnostic test accuracy study

KW - diastolic blood pressure

KW - disease predisposition

KW - disease severity

KW - female

KW - gene mutation

KW - genetic association

KW - genetic association study

KW - genetic profile

KW - genetic risk score

KW - genome-wide association study

KW - genotype

KW - genotype phenotype correlation

KW - genotyping

KW - heart failure

KW - hemodynamics

KW - high throughput sequencing

KW - human

KW - major clinical study

KW - male

KW - middle aged

KW - mortality

KW - mortality risk

KW - peripheral arterial disease

KW - pleura effusion

KW - population

KW - quality control

KW - receiver operating characteristic

KW - risk factor

KW - Russian (people)

KW - septic shock

KW - sequence analysis

KW - aged

KW - epidemiology

KW - genetics

KW - multifactorial inheritance

KW - Russian Federation

KW - Severe acute respiratory syndrome coronavirus 2

KW - severity of illness index

KW - single nucleotide polymorphism

KW - virology

KW - Adult

KW - Aged

KW - Case-Control Studies

KW - Female

KW - Genetic Predisposition to Disease

KW - Genetic Risk Score

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Middle Aged

KW - Multifactorial Inheritance

KW - Polymorphism, Single Nucleotide

KW - Risk Factors

KW - Russia

KW - SARS-CoV-2

KW - Severity of Illness Index

U2 - 10.1017/S0950268824001778

DO - 10.1017/S0950268824001778

M3 - статья

VL - 153

JO - Epidemiology and Infection

JF - Epidemiology and Infection

SN - 0950-2688

ER -