Glessner Joseph T, Chang Xiao, Mentch Frank, Qu Huiqi, Abrams Debra J, Thomas Alexandria, Sleiman Patrick M A, Hakonarson Hakon
Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Front Genet. 2022 Aug 16;13:928466. doi: 10.3389/fgene.2022.928466. eCollection 2022.
The uptick in SARS-CoV-2 infection has resulted in a worldwide COVID-19 pandemic, which has created troublesome health and economic problems. We performed case-control meta-analyses in both African and European ethnicity COVID-19 disease cases based on laboratory test and phenotypic criteria. The cases had laboratory-confirmed SARS-CoV-2 infection. We uniquely investigated COVID infection genetics in a pediatric population. Our cohort has a large African ancestry component, also unique to our study. We tested for genetic variant association in 498 cases vs. 1,533 controls of African ancestry and 271 cases vs. 855 controls of European ancestry. We acknowledge that the sample size is relatively small, owing to the low prevalence of COVID infection among pediatric individuals. COVID-19 cases averaged 13 years of age. Pediatric genetic studies enhance the ability to detect genetic associations with a limited possible environment impact. Our findings support the notion that some genetic variants, most notably at the SEMA6D, FMN1, ACTN1, PDS5B, NFIA, ADGRL3, MMP27, TENM3, SPRY4, MNS1, and RSU1 loci, play a role in COVID-19 infection susceptibility. The pediatric cohort also shows nominal replication of previously reported adult study results: CCR9, CXCR6, FYCO1, LZTFL1, TDGF1, CCR1, CCR2, CCR3, CCR5, MAPT-AS1, and IFNAR2 gene variants. Reviewing the biological roles of genes implicated here, NFIA looks to be the most interesting as it binds to a palindromic sequence observed in both viral and cellular promoters and in the adenovirus type 2 origin of replication.
SARS-CoV-2感染的上升导致了全球范围内的COVID-19大流行,这带来了棘手的健康和经济问题。我们基于实验室检测和表型标准,对非洲和欧洲种族的COVID-19疾病病例进行了病例对照荟萃分析。这些病例经实验室确诊为SARS-CoV-2感染。我们专门在儿科人群中研究了COVID感染遗传学。我们的队列中有很大一部分是非洲血统,这也是我们研究的独特之处。我们对498例非洲血统病例与1533例对照以及271例欧洲血统病例与855例对照进行了基因变异关联测试。我们承认,由于儿科个体中COVID感染的患病率较低,样本量相对较小。COVID-19病例的平均年龄为13岁。儿科遗传学研究增强了在有限的可能环境影响下检测基因关联的能力。我们的研究结果支持这样一种观点,即一些基因变异,最显著的是在SEMA6D、FMN1、ACTN1、PDS5B、NFIA、ADGRL3、MMP27、TENM3、SPRY4、MNS1和RSU1基因座,在COVID-19感染易感性中起作用。儿科队列还显示出对先前报道的成人研究结果的名义性重复:CCR9、CXCR6、FYCO1、LZTFL1、TDGF1、CCR1、CCR2、CCR3、CCR5、MAPT-AS1和IFNAR2基因变异。审视这里涉及的基因的生物学作用,NFIA似乎是最有趣的,因为它与在病毒和细胞启动子以及腺病毒2型复制起点中观察到的回文序列结合。