Evaluation and limitations of different approaches among COVID-19 fatal cases using whole-exome sequencing data

BMC Genomics

Research

Peter Radvak¹  Tomas Szemes²  Rastislav Hekel³  Natalia Forgacova⁴  Jan Radvanszky⁵  Tatiana Sedlackova⁶  Jaroslav Budis⁷  Zuzana Pos⁸  Kristina Mikus Kuracinova⁹  Lucia Krivosikova⁹  Pavel Babal⁹  Pavol Janega⁹  Juraj Gazdarica^1,10  Zuzana Holesova^1,11 

[1] Comenius University Science Park, 841 04, Bratislava, Slovakia;Comenius University Science Park, 841 04, Bratislava, Slovakia;Faculty of Natural Sciences, Comenius University, 841 04, Bratislava, Slovakia;Geneton Ltd, 841 04, Bratislava, Slovakia;Comenius University Science Park, 841 04, Bratislava, Slovakia;Faculty of Natural Sciences, Comenius University, 841 04, Bratislava, Slovakia;Geneton Ltd, 841 04, Bratislava, Slovakia;Slovak Centre of Scientific and Technical Information, 811 04, Bratislava, Slovakia;Comenius University Science Park, 841 04, Bratislava, Slovakia;Faculty of Natural Sciences, Comenius University, 841 04, Bratislava, Slovakia;Institute of Clinical and Translational Research, Biomedical Research Centre, Slovak Academy of Sciences, 845 05, Bratislava, Slovakia;Comenius University Science Park, 841 04, Bratislava, Slovakia;Faculty of Natural Sciences, Comenius University, 841 04, Bratislava, Slovakia;Institute of Clinical and Translational Research, Biomedical Research Centre, Slovak Academy of Sciences, 845 05, Bratislava, Slovakia;Geneton Ltd, 841 04, Bratislava, Slovakia;Comenius University Science Park, 841 04, Bratislava, Slovakia;Geneton Ltd, 841 04, Bratislava, Slovakia;Comenius University Science Park, 841 04, Bratislava, Slovakia;Geneton Ltd, 841 04, Bratislava, Slovakia;Slovak Centre of Scientific and Technical Information, 811 04, Bratislava, Slovakia;Comenius University Science Park, 841 04, Bratislava, Slovakia;Institute of Clinical and Translational Research, Biomedical Research Centre, Slovak Academy of Sciences, 845 05, Bratislava, Slovakia;Geneton Ltd, 841 04, Bratislava, Slovakia;Department of Pathology, Faculty of Medicine, Comenius University, 813 72, Bratislava, Slovakia;Faculty of Natural Sciences, Comenius University, 841 04, Bratislava, Slovakia;Geneton Ltd, 841 04, Bratislava, Slovakia;Slovak Centre of Scientific and Technical Information, 811 04, Bratislava, Slovakia;Geneton Ltd, 841 04, Bratislava, Slovakia;

关键词: SARS-CoV-2;    COVID-19;    Whole-exome sequencing;    Genetic association;    Polymorphisms;    Gnomad;    Non-invasive prenatal testing;   

DOI  :  10.1186/s12864-022-09084-5

 received in 2022-02-28, accepted in 2022-12-15,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundCOVID-19 caused by the SARS-CoV-2 infection may result in various disease symptoms and severity, ranging from asymptomatic, through mildly symptomatic, up to very severe and even fatal cases. Although environmental, clinical, and social factors play important roles in both susceptibility to the SARS-CoV-2 infection and progress of COVID-19 disease, it is becoming evident that both pathogen and host genetic factors are important too. In this study, we report findings from whole-exome sequencing (WES) of 27 individuals who died due to COVID-19, especially focusing on frequencies of DNA variants in genes previously associated with the SARS-CoV-2 infection and the severity of COVID-19.ResultsWe selected the risk DNA variants/alleles or target genes using four different approaches: 1) aggregated GWAS results from the GWAS Catalog; 2) selected publications from PubMed; 3) the aggregated results of the Host Genetics Initiative database; and 4) a commercial DNA variant annotation/interpretation tool providing its own knowledgebase. We divided these variants/genes into those reported to influence the susceptibility to the SARS-CoV-2 infection and those influencing the severity of COVID-19. Based on the above, we compared the frequencies of alleles found in the fatal COVID-19 cases to the frequencies identified in two population control datasets (non-Finnish European population from the gnomAD database and genomic frequencies specific for the Slovak population from our own database). When compared to both control population datasets, our analyses indicated a trend of higher frequencies of severe COVID-19 associated risk alleles among fatal COVID-19 cases. This trend reached statistical significance specifically when using the HGI-derived variant list. We also analysed other approaches to WES data evaluation, demonstrating its utility as well as limitations.ConclusionsAlthough our results proved the likely involvement of host genetic factors pointed out by previous studies looking into severity of COVID-19 disease, careful considerations of the molecular-testing strategies and the evaluated genomic positions may have a strong impact on the utility of genomic testing.

【 授权许可】

CC BY   
© The Author(s) 2023

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