tetano
Editor, Senior Moderator
Nat Genet
. 2026 Jan 22.
doi: 10.1038/s41588-025-02484-9. Online ahead of print.
Central role of glycosylation processes in human genetic susceptibility to SARS-CoV-2 infections with Omicron variants
Frank Geller[SUP] 1 2 3 [/SUP], Xiaoping Wu[SUP] 4 5 [/SUP], Vilma Lammi[SUP] 6 7 [/SUP], Erik Abner[SUP] 8 [/SUP], Jesse Tyler Valliere[SUP] 7 9 [/SUP], Katerina Nastou[SUP] 4 [/SUP], Angus Burns[SUP] 7 9 [/SUP], Morten Rasmussen[SUP] 10 [/SUP], Niklas Worm Andersson[SUP] 4 [/SUP], Liam Quinn[SUP] 11 [/SUP]; DBDS Genomic Consortium; Bitten Aagaard[SUP] 12 [/SUP], Karina Banasik[SUP] 13 14 [/SUP], Sofie Bliddal[SUP] 13 15 [/SUP], Lasse Boding[SUP] 16 [/SUP], Søren Brunak[SUP] 14 [/SUP], Nanna Brøns[SUP] 5 [/SUP], Jonas Bybjerg-Grauholm[SUP] 17 [/SUP], Lea Arregui Nordahl Christoffersen[SUP] 11 18 [/SUP], Maria Didriksen[SUP] 5 19 [/SUP], Khoa Manh Dinh[SUP] 5 20 [/SUP], Christian Erikstrup[SUP] 20 21 [/SUP], Ulla Feldt-Rasmussen[SUP] 15 22 [/SUP], Kirsten Grønbæk[SUP] 22 23 24 [/SUP], Kathrine Agergård Kaspersen[SUP] 20 [/SUP], Christina Mikkelsen[SUP] 5 25 [/SUP], Claus Henrik Nielsen[SUP] 26 [/SUP], Henriette Svarre Nielsen[SUP] 13 22 [/SUP], Susanne Dam Nielsen[SUP] 27 [/SUP], Janna Nissen[SUP] 5 [/SUP], Celia Burgos Sequeros[SUP] 14 [/SUP], Niels Tommerup[SUP] 28 [/SUP], Henrik Ullum[SUP] 29 [/SUP]; Estonian Biobank Research Team; FinnGen; Lampros Spiliopoulos[SUP] 4 [/SUP], Peter Bager[SUP] 4 [/SUP], Anders Hviid[SUP] 4 30 [/SUP], Erik Sørensen[SUP] 5 [/SUP], Ole Birger Pedersen[SUP] 11 22 [/SUP], Jacqueline M Lane[SUP] 7 9 [/SUP], Ria Lassaunière[SUP] 10 [/SUP], Hanna M Ollila[SUP] 6 31 [/SUP], Sisse Rye Ostrowski[SUP] 5 22 [/SUP], Bjarke Feenstra[SUP] 4 17 5 32 [/SUP]
Affiliations
The host genetics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have previously been studied based on cases from the earlier waves of the pandemic in 2020 and 2021, identifying 51 genomic loci associated with infection and/or severity. SARS-CoV-2 has shown rapid sequence evolution, increasing transmissibility, particularly for Omicron variants, which raises the question of whether this affected the host genetic factors. We performed a genome-wide association study of SARS-CoV-2 infection with Omicron variants, including more than 150,000 cases from four cohorts. We identified 13 genome-wide significant loci, of which only five were previously described as associated with SARS-CoV-2 infection. The strongest signal was a single nucleotide polymorphism in an intron of ST6GAL1, a gene affecting immune development and function, connected to three other associated loci (harboring MUC1, MUC5AC and MUC16) through O-glycan biosynthesis. Our study provides robust evidence for individual genetic variation related to glycosylation, translating into susceptibility to SARS-CoV-2 infections with Omicron variants.
. 2026 Jan 22.
doi: 10.1038/s41588-025-02484-9. Online ahead of print.
Central role of glycosylation processes in human genetic susceptibility to SARS-CoV-2 infections with Omicron variants
Frank Geller[SUP] 1 2 3 [/SUP], Xiaoping Wu[SUP] 4 5 [/SUP], Vilma Lammi[SUP] 6 7 [/SUP], Erik Abner[SUP] 8 [/SUP], Jesse Tyler Valliere[SUP] 7 9 [/SUP], Katerina Nastou[SUP] 4 [/SUP], Angus Burns[SUP] 7 9 [/SUP], Morten Rasmussen[SUP] 10 [/SUP], Niklas Worm Andersson[SUP] 4 [/SUP], Liam Quinn[SUP] 11 [/SUP]; DBDS Genomic Consortium; Bitten Aagaard[SUP] 12 [/SUP], Karina Banasik[SUP] 13 14 [/SUP], Sofie Bliddal[SUP] 13 15 [/SUP], Lasse Boding[SUP] 16 [/SUP], Søren Brunak[SUP] 14 [/SUP], Nanna Brøns[SUP] 5 [/SUP], Jonas Bybjerg-Grauholm[SUP] 17 [/SUP], Lea Arregui Nordahl Christoffersen[SUP] 11 18 [/SUP], Maria Didriksen[SUP] 5 19 [/SUP], Khoa Manh Dinh[SUP] 5 20 [/SUP], Christian Erikstrup[SUP] 20 21 [/SUP], Ulla Feldt-Rasmussen[SUP] 15 22 [/SUP], Kirsten Grønbæk[SUP] 22 23 24 [/SUP], Kathrine Agergård Kaspersen[SUP] 20 [/SUP], Christina Mikkelsen[SUP] 5 25 [/SUP], Claus Henrik Nielsen[SUP] 26 [/SUP], Henriette Svarre Nielsen[SUP] 13 22 [/SUP], Susanne Dam Nielsen[SUP] 27 [/SUP], Janna Nissen[SUP] 5 [/SUP], Celia Burgos Sequeros[SUP] 14 [/SUP], Niels Tommerup[SUP] 28 [/SUP], Henrik Ullum[SUP] 29 [/SUP]; Estonian Biobank Research Team; FinnGen; Lampros Spiliopoulos[SUP] 4 [/SUP], Peter Bager[SUP] 4 [/SUP], Anders Hviid[SUP] 4 30 [/SUP], Erik Sørensen[SUP] 5 [/SUP], Ole Birger Pedersen[SUP] 11 22 [/SUP], Jacqueline M Lane[SUP] 7 9 [/SUP], Ria Lassaunière[SUP] 10 [/SUP], Hanna M Ollila[SUP] 6 31 [/SUP], Sisse Rye Ostrowski[SUP] 5 22 [/SUP], Bjarke Feenstra[SUP] 4 17 5 32 [/SUP]
Affiliations
- PMID: 41571831
- DOI: 10.1038/s41588-025-02484-9
The host genetics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have previously been studied based on cases from the earlier waves of the pandemic in 2020 and 2021, identifying 51 genomic loci associated with infection and/or severity. SARS-CoV-2 has shown rapid sequence evolution, increasing transmissibility, particularly for Omicron variants, which raises the question of whether this affected the host genetic factors. We performed a genome-wide association study of SARS-CoV-2 infection with Omicron variants, including more than 150,000 cases from four cohorts. We identified 13 genome-wide significant loci, of which only five were previously described as associated with SARS-CoV-2 infection. The strongest signal was a single nucleotide polymorphism in an intron of ST6GAL1, a gene affecting immune development and function, connected to three other associated loci (harboring MUC1, MUC5AC and MUC16) through O-glycan biosynthesis. Our study provides robust evidence for individual genetic variation related to glycosylation, translating into susceptibility to SARS-CoV-2 infections with Omicron variants.