Comenius University Science Park, Bratislava, 841 04, Slovakia.
Faculty of Natural Sciences, Comenius University, Bratislava, 841 04, Slovakia.
BMC Genomics. 2023 Jan 10;24(1):12. doi: 10.1186/s12864-022-09084-5.
COVID-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.
We 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.
Although 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.
由 SARS-CoV-2 感染引起的 COVID-19 可能导致各种疾病症状和严重程度，从无症状到轻度症状，到非常严重甚至致命病例不等。尽管环境、临床和社会因素在 SARS-CoV-2 感染易感性和 COVID-19 疾病进展中起着重要作用，但病原体和宿主遗传因素也很重要。在这项研究中，我们报告了对 27 名因 COVID-19 死亡的个体进行全外显子组测序（WES）的结果，特别是重点关注了先前与 SARS-CoV-2 感染和 COVID-19 严重程度相关的基因中的 DNA 变体频率。
我们使用了四种不同的方法选择了风险 DNA 变体/等位基因或靶基因：1）从 GWAS 目录中汇总 GWAS 结果；2）从 PubMed 中选择出版物；3）宿主遗传学倡议数据库的汇总结果；4）提供自己知识库的商业 DNA 变体注释/解释工具。我们将这些变体/基因分为那些报道影响 SARS-CoV-2 感染易感性的和那些影响 COVID-19 严重程度的基因。基于上述方法，我们将在致命 COVID-19 病例中发现的等位基因频率与两个人群对照数据集（gnomAD 数据库中的非芬兰欧洲人群和我们自己数据库中特定于斯洛伐克人群的基因组频率）进行比较。与两个对照人群数据集相比，我们的分析表明，致命 COVID-19 病例中严重 COVID-19 相关风险等位基因的频率呈上升趋势。当使用 HGI 衍生的变体列表时，这种趋势具有统计学意义。我们还分析了 WES 数据评估的其他方法，证明了它的实用性和局限性。
尽管我们的结果证明了宿主遗传因素可能参与了以前研究中指出的 COVID-19 疾病严重程度，但对分子检测策略和评估的基因组位置的仔细考虑可能会对基因组检测的实用性产生重大影响。
