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Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
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COVID-19 in pediatrics: Genetic susceptibility
Joseph T Glessner1,2, Xiao Chang1, Frank Mentch1
1Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Frontiers in Genetics
|September 2, 2022
Summary
This study identified genetic variants associated with COVID-19 susceptibility in children. Key genes like NFIA were implicated, offering insights into the pandemic
Area of Science:
- Genetics
- Infectious Diseases
- Pediatrics
Background:
- The COVID-19 pandemic caused by SARS-CoV-2 has led to significant global health and economic challenges.
- Understanding the genetic factors influencing COVID-19 susceptibility is crucial for public health strategies.
- Pediatric populations represent a unique cohort for genetic studies due to a potentially less confounded environmental impact.
Purpose of the Study:
- To investigate genetic associations with COVID-19 infection susceptibility in pediatric populations of African and European ancestry.
- To identify specific genetic variants that may confer risk or protection against SARS-CoV-2 infection in children.
- To explore potential replication of previously identified adult genetic associations within a pediatric cohort.
Main Methods:
- Case-control meta-analyses were conducted on laboratory-confirmed COVID-19 pediatric cases and controls.
- Genetic variant association testing was performed on cohorts of African ancestry (498 cases vs. 1,533 controls) and European ancestry (271 cases vs. 855 controls).
- Phenotypic criteria and laboratory test results were used for case definition.
Main Results:
- Several genetic loci, including SEMA6D, FMN1, ACTN1, PDS5B, NFIA, ADGRL3, MMP27, TENM3, SPRY4, MNS1, and RSU1, were associated with COVID-19 susceptibility.
- Nominal replication of previously reported adult genetic variants (e.g., CCR9, CXCR6, LZTFL1, IFNAR2) was observed in the pediatric cohort.
- The gene NFIA showed particular interest due to its binding properties to viral and cellular promoter sequences.
Conclusions:
- Specific genetic variants play a role in determining susceptibility to COVID-19 infection, even in pediatric individuals.
- The findings highlight the importance of genetic factors across different ancestries and age groups.
- Further research into genes like NFIA may elucidate mechanisms of viral infection and host response.
Keywords:
COVID-19GWASdiverse populationsgenome-wide association studypediatricsstatistical genetics and genomicsMore Related Videos
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