TY - JOUR
T1 - Genome-Wide Association study of susceptibility to respiratory syncytial virus hospitalization in young children < 5 years of age
AU - Egeskov-Cavling, Amanda Marie
AU - van Wijhe, Maarten
AU - Yakimov, Victor
AU - Johannesen, Caroline Klint
AU - Pollard, Andrew J
AU - Trebbien, Ramona
AU - Bybjerg-Grauholm, Jonas
AU - Fischer, Thea Kølsen
AU - RESCEU Investigators
N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85195492191&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiad370
DO - 10.1093/infdis/jiad370
M3 - Journal article
C2 - 37666001
SN - 0022-1899
VL - 230
SP - e333-e341
JO - The Journal of infectious diseases
JF - The Journal of infectious diseases
IS - 2
ER -