Genome-Wide Association study of susceptibility to respiratory syncytial virus hospitalization in young children < 5 years of age

Amanda Marie Egeskov-Cavling; Maarten van Wijhe; Victor Yakimov; Caroline Klint Johannesen; Andrew J Pollard; Ramona Trebbien; Jonas Bybjerg-Grauholm; Thea Kølsen Fischer; RESCEU investigators

doi:10.1093/infdis/jiad370

Genome-Wide Association study of susceptibility to respiratory syncytial virus hospitalization in young children < 5 years of age

J Infect Dis. 2023 Sep 4:jiad370. doi: 10.1093/infdis/jiad370. Online ahead of print.

Authors

Collaborators

Affiliations

¹ Dept of Virus and Microbiological Special Diagnostics, Statens Serum Institut, Copenhagen, Denmark.
² Dept of Clinical Research, Nordsjællands Hospital, Hilleroed, Denmark.
³ Dept of Science and Environment, Roskilde University, Roskilde, Denmark.
⁴ Neonatal Genetics, Statens Serum Institut, Copenhagen, Denmark.
⁵ Oxford Vaccine Group, Department of Pediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
⁶ Dept of Public Health, University of Copenhagen, Denmark.

PMID: 37666001
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 two Danish cohorts. We compared SNPs from 1786 children hospitalized with RSV to 45,060 controls without a RSV-coded hospitalization. We performed gene-based testing, tissue-enrichment, gene-set enrichment, and a meta-analysis of the two 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 one cohort, however, we failed to replicate any signals in both cohorts.

Conclusion: 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: Genetic association studies; Genome-Wide Association Study; RSV; respiratory syncytial virus.