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.

The authors have declared no competing interest.

This study did not receive any funding.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study used ONLY openly available human data that were originally located at UKBB, FinnGen and COVID HGI.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

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All data produced in the present study are available upon reasonable request to the authors.