{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T09:41:17Z","timestamp":1792489277979,"version":"4.5.0"},"reference-count":73,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971706"],"award-info":[{"award-number":["81971706"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Influenza Resp Viruses"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Influenza remains a significant global health burden, potentially leading to hospitalization and mortality. Although previous studies have explored genetic susceptibility to influenza infection, the genetic basis of influenza hospitalization and its relationship with respiratory diseases like COVID\u201019 remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed a binary GWAS of hospitalized influenza using UK Biobank data (UKBB; 1037 cases\/404,108 controls) and then meta\u2010analyzed results with the FinnGen GWAS, yielding 11,171 cases and 782,400 controls. A time\u2010to\u2010event GWAS in UKBB was also performed to identify genetic factors underlying the timing (age) of first influenza hospitalization.\n                      <jats:italic>p<\/jats:italic>\n                      \u2010values from both analyses were integrated by the harmonic mean\n                      <jats:italic>p<\/jats:italic>\n                      \u2010value (HMP) method to enhance association detection. Further differentiation and colocalization analyses with COVID\u201019 investigated their distinct and shared genetic features. An integrative framework combining functional annotations, multi\u2010omics analyses, and phenome\u2010wide scans prioritized key risk and differential genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The binary GWAS meta\u2010analysis identified three loci (\n                      <jats:italic>ST6GAL1<\/jats:italic>\n                      ,\n                      <jats:italic>AASDHPPT<\/jats:italic>\n                      ,\n                      <jats:italic>SPATS2L<\/jats:italic>\n                      ) associated with hospitalization risk. The time\u2010to\u2010event GWAS recognized\n                      <jats:italic>UGT2B4<\/jats:italic>\n                      as linked to hospitalization timing. HMP analysis, which combines evidence across the binary and time\u2010to\u2010event analyses, identified ST6GAL1 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20093\u2009\u00d7\u200910\n                      <jats:sup>\u22129<\/jats:sup>\n                      ) and UGT2B4 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20093.63\u2009\u00d7\u200910\n                      <jats:sup>\u22128<\/jats:sup>\n                      ) as genome\u2010wide significant; however, each signal was driven predominantly by one component test, ST6GAL1 by the binary meta\u2010analysis (meta\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20091.5\u2009\u00d7\u200910\n                      <jats:sup>\u22129<\/jats:sup>\n                      ), and UGT2B4 by the time\u2010to\u2010event analysis (SPACox\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20091.82\u2009\u00d7\u200910\n                      <jats:sup>\u22128<\/jats:sup>\n                      ), rather than showing independent support from both analyses. Differentiation analysis identified 29 loci and two tissues distinguishing influenza from COVID\u201019, whereas analysis of shared association signals (cofdr) highlighted candidate shared genetic factors, including\n                      <jats:italic>ST6GAL1<\/jats:italic>\n                      and\n                      <jats:italic>ICAM5<\/jats:italic>\n                      (gene\u2010level PPA\u2009\u2265\u20090.9).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study uncovers the genetic architectures of hospitalized influenza. It also highlights genetic differences and similarities with COVID\u201019, providing hypothesis\u2010generating insights that may inform future functional and therapeutic research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/irv.70334","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:49:51Z","timestamp":1792133391000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genome\u2010Wide Association Studies of Hospitalized Influenza Identify Four Risk Loci and Reveal Shared and Unique Genetic Factors Compared With COVID\u201019"],"prefix":"10.1111","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4657-4889","authenticated-orcid":false,"given":"Xiao","family":"Xue","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences The Chinese University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaning","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The Chinese University of Hong Kong  Hong Kong SAR China"},{"name":"School of Medical Technology and Information Engineering Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Ping","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The Chinese University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pui\u2010Ching","family":"Chan","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The Chinese University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7102-833X","authenticated-orcid":false,"given":"Hon\u2010Cheong","family":"So","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The Chinese University of Hong Kong  Hong Kong SAR China"},{"name":"Department of Psychiatry The Chinese University of Hong Kong  Hong Kong SAR China"},{"name":"CUHK Shenzhen Research Institute  Shenzhen China"},{"name":"Margaret K. 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Cheung Research Centre for Management of Parkinsonism The Chinese University of Hong Kong  Hong Kong SAR China"},{"name":"Brain and Mind Institute The Chinese University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"World Health Organization \u201cInfluenza (Seasonal) \u201d (2025) retrieved April 3 2025 https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/influenza\u2010(seasonal)."},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2020.09.048"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/irv.12504"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.07.066"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10921"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis378"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-024-01844-1"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1631\/jzus.B2000479"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001779"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13742-015-0047-8"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00954-4"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btab665"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.06.003"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq340"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt500"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1814092116"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3211"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01261-5"},{"key":"e_1_2_12_20_1","doi-asserted-by":"crossref","unstructured":"C. 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