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. 2024 Mar 1;229(Supplement_1):S112-S119.
doi: 10.1093/infdis/jiae029.

A Genome-Wide Association Study of Respiratory Syncytial Virus Infection Severity in Infants

Mari Johnson  1   2 , Irina Chelysheva  1   2 , Deniz Öner  3 , Joseph McGinley  1   2 , Gu-Lung Lin  1   2 , Daniel O'Connor  1   2 , Hannah Robinson  1   2 , Simon B Drysdale  1   2 , Emma Gammin  1   2 , Sophie Vernon  1   2 , Jill Muller  1   2 , Helen Wolfenden  4 , Sharon Westcar  4 , Lazarus Anguvaa  5 , Ryan S Thwaites  6 , Louis Bont  7 , Joanne Wildenbeest  7 , Federico Martinón-Torres  8   9   10 , Jeroen Aerssens  3 , Peter J M Openshaw  6 , Andrew J Pollard  1   2
Affiliations

A Genome-Wide Association Study of Respiratory Syncytial Virus Infection Severity in Infants

Mari Johnson et al. J Infect Dis. .

Abstract

Background: Respiratory syncytial virus (RSV) is a significant cause of infant morbidity and mortality worldwide. Most children experience at least one 1 RSV infection by the age of two 2 years, but not all develop severe disease. However, the understanding of genetic risk factors for severe RSV is incomplete. Consequently, we conducted a genome-wide association study of RSV severity.

Methods: Disease severity was assessed by the ReSVinet scale, in a cohort of 251 infants aged 1 week to 1 year. Genotyping data were collected from multiple European study sites as part of the RESCEU Consortium. Linear regression models were used to assess the impact of genotype on RSV severity and gene expression as measured by microarray.

Results: While no SNPs reached the genome-wide statistical significance threshold (P < 5 × 10-8), we identified 816 candidate SNPs with a P-value of <1 × 10-4. Functional annotation of candidate SNPs highlighted genes relevant to neutrophil trafficking and cytoskeletal functions, including LSP1 and RAB27A. Moreover, SNPs within the RAB27A locus significantly altered gene expression (false discovery rate, FDR P < .05).

Conclusions: These findings may provide insights into genetic mechanisms driving severe RSV infection, offering biologically relevant information for future investigations.

Keywords: GWAS; RSV; eQTL; infection; inflammation.

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Conflict of interest statement

Potential conflicts of interest. F. M.-T. and P. J. M. O. have received honoraria from the GSK group of companies, Pfizer, Sanofi Pasteur, MSD, Seqirus, AstraZeneca, Moderna, and Janssen for taking part in advisory boards and expert meetings and for acting as a speaker in congresses outside the scope of the submitted work. F. M.-T. has also acted as principal investigator in randomized controlled trials of the aforementioned companies as well as Ablynx, Gilead, Regeneron, Roche, Abbott, Novavax, and MedImmune, with honoraria paid to his institution. S. B. D. has received honoraria from MSD and Sanofi for taking part in RSV advisory boards and has provided consultancy and/or investigator roles in relation to product development for Janssen, AstraZeneca, Pfizer, Moderna, Valneva, MSD, iLiAD, and Sanofi with fees paid to St George's, University of London. S. B. D. is a member of the UK Department of Health and Social Care's Joint Committee on Vaccination and Immunisation RSV subcommittee and Medicines and Healthcare Products Regulatory Agency's Paediatric Medicine Expert Advisory Group, but the reviews expressed herein do not necessarily represent any of those groups. A. J. P. is chair of the Department of Health and Social Care's Joint Committee on Vaccination and Immunisation. J. W. participated in the advisory board of Janssen and Sanofi with fees paid to University Medical Centre Utrecht and has been an investigator for clinical trials sponsored by pharmaceutical companies including AstraZeneca, Merck, Pfizer, Sanofi, and Janssen. All funds have been paid to University Medical Centre Utrecht. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.