Genome-wide association studies of hospitalized influenza identify 4 risk loci and a relationship with COVID-19

Influenza remains a significant global health burden, with the potential for severe complications and mortality. This study investigates the genetic architecture of hospitalized influenza and explores its shared and distinct genetic factors with hospitalized COVID-19. A binary GWAS of hospitalized influenza using UK Biobank data, followed by meta-analysis with FinnGen, identified three risk loci: ST6GAL1, AASDHPPT, and SPATS2L. Additionally, a time-to-event GWAS revealed a novel susceptibility locus, UGT2B4. Further differentiation analysis with hospitalized COVID-19 identified 29 differentially associated loci, highlighting their distinct genetic architectures. Colocalization analysis uncovered shared genetic mechanisms, with ST6GAL1 and ICAM5 emerging as key candidates. These findings provide new insights into the genetic basis of influenza and its relationship with COVID-19, offering potential therapeutic targets and avenues for personalized medicine.