Genome-wide Association Study of Susceptibility to Respiratory Syncytial Virus Hospitalization in Young Children <5 Years of age

J Infect Dis. 2024 Aug 16;230(2):e333-e341. doi: 10.1093/infdis/jiad370.

Abstract

Background: Worldwide, respiratory syncytial virus (RSV) infections are among the most common causes of infant hospitalization. Host genetic factors influencing the risk and severity of RSV infection are not well known.

Methods: We conducted a genome-wide association study (GWAS) to investigate single-nucleotide polymorphisms (SNPs) associated with severe RSV infections using a nested case-control design based on 2 Danish cohorts. We compared SNPs from 1786 children hospitalized with RSV to 45 060 controls without an RSV-coded hospitalization. We performed gene-based testing, tissue enrichment, gene-set enrichment, and a meta-analysis of the 2 cohorts. Finally, an analysis of potential associations between the severity of RSV infection and genetic markers was performed.

Results: We did not detect any significant genome-wide associations between SNPs and RSV infection or the severity of RSV. We did find potential loci associated with RSV infections on chromosome 5 in 1 cohort but failed to replicate any signals in both cohorts.

Conclusions: Despite being the largest GWAS of severe RSV infection, we did not detect any genome-wide significant loci. This may be an indication of a lack of power or an absence of signal. Future studies might include mild illness and need to be larger to detect any significant associations.

Keywords: RSV; genetic association studies; genome-wide association study; respiratory syncytial virus.

MeSH terms

  • Case-Control Studies
  • Child, Preschool
  • Denmark / epidemiology
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Hospitalization* / statistics & numerical data
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Polymorphism, Single Nucleotide*
  • Respiratory Syncytial Virus Infections* / epidemiology
  • Respiratory Syncytial Virus Infections* / genetics
  • Respiratory Syncytial Virus Infections* / virology
  • Respiratory Syncytial Virus, Human / genetics

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