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

Mari Johnson; Irina Chelysheva; Deniz Öner; Joseph McGinley; Gu-Lung Lin; Daniel O'Connor; Hannah Robinson; Simon B Drysdale; Emma Gammin; Sophie Vernon; Jill Muller; Helen Wolfenden; Sharon Westcar; Lazarus Anguvaa; Ryan S Thwaites; Louis Bont; Joanne Wildenbeest; Federico Martinón-Torres; Jeroen Aerssens; Peter J M Openshaw; Andrew J Pollard

doi:10.1093/infdis/jiae029

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

Mari Johnson^*, Irina Chelysheva, Deniz Öner, Joseph McGinley, Gu-Lung Lin, Daniel O'Connor, Hannah Robinson, Simon B Drysdale, Emma Gammin, Sophie Vernon, Jill Muller, Helen Wolfenden, Sharon Westcar, Lazarus Anguvaa, Ryan S Thwaites, Louis Bont, Joanne Wildenbeest, Federico Martinón-Torres, Jeroen Aerssens, Peter J M OpenshawAndrew J Pollard

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	S112-S119
Journal	The Journal of infectious diseases
Volume	229
Issue number	Supplement_1
DOIs	https://doi.org/10.1093/infdis/jiae029
Publication status	Published - 15 Mar 2024

Keywords

GWAS
RSV
eQTL
infection
inflammation

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Johnson, M., Chelysheva, I., Öner, D., McGinley, J., Lin, G.-L., O'Connor, D., Robinson, H., Drysdale, S. B., Gammin, E., Vernon, S., Muller, J., Wolfenden, H., Westcar, S., Anguvaa, L., Thwaites, R. S., Bont, L., Wildenbeest, J., Martinón-Torres, F., Aerssens, J., ... Pollard, A. J. (2024). A Genome-Wide Association Study of Respiratory Syncytial Virus Infection Severity in Infants. The Journal of infectious diseases, 229(Supplement_1), S112-S119. https://doi.org/10.1093/infdis/jiae029

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title = "A Genome-Wide Association Study of Respiratory Syncytial Virus Infection Severity in Infants",

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",

author = "Mari Johnson and Irina Chelysheva and Deniz {\"O}ner and Joseph McGinley and Gu-Lung Lin and Daniel O'Connor and Hannah Robinson and Drysdale, {Simon B} and Emma Gammin and Sophie Vernon and Jill Muller and Helen Wolfenden and Sharon Westcar and Lazarus Anguvaa and Thwaites, {Ryan S} and Louis Bont and Joanne Wildenbeest and Federico Martin{\'o}n-Torres and Jeroen Aerssens and Openshaw, {Peter J M} and Pollard, {Andrew J}",

year = "2024",

month = mar,

day = "15",

doi = "10.1093/infdis/jiae029",

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Johnson, M, Chelysheva, I, Öner, D, McGinley, J, Lin, G-L, O'Connor, D, Robinson, H, Drysdale, SB, Gammin, E, Vernon, S, Muller, J, Wolfenden, H, Westcar, S, Anguvaa, L, Thwaites, RS, Bont, L , Wildenbeest, J, Martinón-Torres, F, Aerssens, J, Openshaw, PJM & Pollard, AJ 2024, 'A Genome-Wide Association Study of Respiratory Syncytial Virus Infection Severity in Infants', The Journal of infectious diseases, vol. 229, no. Supplement_1, pp. S112-S119. https://doi.org/10.1093/infdis/jiae029

TY - JOUR

T1 - A Genome-Wide Association Study of Respiratory Syncytial Virus Infection Severity in Infants

AU - Johnson, Mari

AU - Chelysheva, Irina

AU - Öner, Deniz

AU - McGinley, Joseph

AU - Lin, Gu-Lung

AU - O'Connor, Daniel

AU - Robinson, Hannah

AU - Drysdale, Simon B

AU - Gammin, Emma

AU - Vernon, Sophie

AU - Muller, Jill

AU - Wolfenden, Helen

AU - Westcar, Sharon

AU - Anguvaa, Lazarus

AU - Thwaites, Ryan S

AU - Bont, Louis

AU - Wildenbeest, Joanne

AU - Martinón-Torres, Federico

AU - Aerssens, Jeroen

AU - Openshaw, Peter J M

AU - Pollard, Andrew J

PY - 2024/3/15

Y1 - 2024/3/15

N2 - 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.

AB - 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.

KW - GWAS

KW - RSV

KW - eQTL

KW - infection

KW - inflammation

UR - http://www.scopus.com/inward/record.url?scp=85186743090&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiae029

DO - 10.1093/infdis/jiae029

M3 - Article

C2 - 38271230

SN - 0022-1899

VL - 229

SP - S112-S119

JO - The Journal of infectious diseases

JF - The Journal of infectious diseases

IS - Supplement_1

ER -

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

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Keywords

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