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. 2022 Aug 16:13:928466.
doi: 10.3389/fgene.2022.928466. eCollection 2022.

COVID-19 in pediatrics: Genetic susceptibility

Joseph T Glessner  1   2 , Xiao Chang  1 , Frank Mentch  1 , Huiqi Qu  1 , Debra J Abrams  1 , Alexandria Thomas  1 , Patrick M A Sleiman  1   2 , Hakon Hakonarson  1   2
Affiliations

COVID-19 in pediatrics: Genetic susceptibility

Joseph T Glessner et al. Front Genet. .

Abstract

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.

Keywords: COVID-19; GWAS; diverse populations; genome-wide association study; pediatrics; statistical genetics and genomics.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Regional significance plot of the 3p21.31 region by LocusZoom (Pruim et al., 2010). The genes CCR9, CXCR6, FYCO1, and LZTFL1 are included in this region. The peak of significance is from the SNP 3:45961470:T:C (rs1601867) at the intronic region of FYCO1.
FIGURE 2
FIGURE 2
Regional significance plot of the 13q13.1 region by LocusZoom (Pruim et al., 2010). The PDS5 cohesin-associated factor B gene (PDS5B) maps to this region. The peak of significance by the meta-analysis is from the SNP 13:32665329:A:C (rs144965594) at the intronic region of PDS5B.
See this image and copyright information in PMC

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