{"doi":"10.1038/s41588-024-01844-1","title":"Genetic risk factors for COVID-19 and influenza are largely distinct","abstract":"Abstract Coronavirus disease 2019 (COVID-19) and influenza are respiratory illnesses caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses, respectively. Both diseases share symptoms and clinical risk factors 1 , but the extent to which these conditions have a common genetic etiology is unknown. This is partly because host genetic risk factors are well characterized for COVID-19 but not for influenza, with the largest published genome-wide association studies for these conditions including >2 million individuals 2 and about 1,000 individuals 3–6 , respectively. Shared genetic risk factors could point to targets to prevent or treat both infections. Through a genetic study of 18,334 cases with a positive test for influenza and 276,295 controls, we show that published COVID-19 risk variants are not associated with influenza. Furthermore, we discovered and replicated an association between influenza infection and noncoding variants in B3GALT5 and ST6GAL1 , neither of which was associated with COVID-19. In vitro small interfering RNA knockdown of ST6GAL1—an enzyme that adds sialic acid to the cell surface, which is used for viral entry—reduced influenza infectivity by 57%. These results mirror the observation that variants that downregulate ACE2 , the SARS-CoV-2 receptor, protect against COVID-19 (ref. 7 ). Collectively, these findings highlight downregulation of key cell surface receptors used for viral entry as treatment opportunities to prevent COVID-19 and influenza.","journal":"Nature Genetics","year":2024,"id":427858,"datarank":0.40620753016533157,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.0,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9519,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":61925,"name":"Anthony Marcketta","orcid":"0000-0001-6356-3343","position":1,"is_corresponding":false},{"id":472766,"name":"Deepika Sharma","orcid":"0000-0002-5840-8266","position":2,"is_corresponding":false},{"id":829960,"name":"Silvio Alessandro Di Gioia","orcid":"0000-0002-7235-5682","position":3,"is_corresponding":false},{"id":1229026,"name":"Samantha Batista","orcid":null,"position":4,"is_corresponding":false},{"id":1228575,"name":"Xiaoman Yang","orcid":"0000-0002-9578-4068","position":5,"is_corresponding":false},{"id":52971,"name":"Gannie Tzoneva","orcid":"0000-0001-5784-7796","position":6,"is_corresponding":false},{"id":343663,"name":"Héctor Martínez","orcid":null,"position":7,"is_corresponding":false},{"id":218093,"name":"Carlo Sidore","orcid":"0000-0001-7504-7477","position":8,"is_corresponding":false},{"id":24981,"name":"Michael D. 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