학술논문
A Genome-Wide Association Study of Respiratory Syncytial Virus Infection Severity in Infants.
Document Type
Article
Author
Johnson, Mari; Chelysheva, Irina; Öner, Deniz; McGinley, Joseph; Lin, Gu-Lung; O'Connor, Daniel; Robinson, Hannah; Drysdale, Simon B; Gammin, Emma; Vernon, Sophie; Muller, Jill; Wolfenden, Helen; Westcar, Sharon; Anguvaa, Lazarus; Thwaites, Ryan S; Bont, Louis; Wildenbeest, Joanne; Martinón-Torres, Federico; Aerssens, Jeroen; Openshaw, Peter J M
Source
Subject
*RESPIRATORY syncytial virus infections
*GENOME-wide association studies
*GENE expression
*INFANTS
*FALSE discovery rate
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Language
ISSN
0022-1899
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. [ABSTRACT FROM AUTHOR]