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

*Corresponding author af dette arbejde

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.

OriginalsprogEngelsk
TidsskriftThe Journal of infectious diseases
Vol/bind230
Udgave nummer2
Sider (fra-til)e333-e341
ISSN0022-1899
DOI
StatusUdgivet - 2024

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