TY - JOUR
T1 - Central role of glycosylation processes in human genetic susceptibility to SARS-CoV-2 infections with Omicron variants
AU - Geller, Frank
AU - Wu, Xiaoping
AU - Lammi, Vilma
AU - Abner, Erik
AU - Valliere, Jesse Tyler
AU - Nastou, Katerina
AU - Burns, Angus
AU - Rasmussen, Morten
AU - Andersson, Niklas Worm
AU - DBDS Genomic Consortium
AU - Quinn, Liam
AU - Aagaard, Bitten
AU - Banasik, Karina
AU - Bliddal, Sofie
AU - Boding, Lasse
AU - Brunak, Søren
AU - Brøns, Nanna
AU - Bybjerg-Grauholm, Jonas
AU - Christoffersen, Lea Arregui Nordahl
AU - Didriksen, Maria
AU - Dinh, Khoa Manh
AU - Erikstrup, Christian
AU - Feldt-Rasmussen, Ulla
AU - Grønbæk, Kirsten
AU - Kaspersen, Kathrine Agergård
AU - Mikkelsen, Christina
AU - Nielsen, Claus Henrik
AU - Nielsen, Henriette Svarre
AU - Nielsen, Susanne Dam
AU - Nissen, Janna
AU - Sequeros, Celia Burgos
AU - Tommerup, Niels
AU - Ullum, Henrik
AU - Estonian Biobank Research Team
AU - FinnGen
AU - Spiliopoulos, Lampros
AU - Bager, Peter
AU - Hviid, Anders
AU - Sørensen, Erik
AU - Pedersen, Ole Birger
AU - Lane, Jacqueline M.
AU - Lassaunière, Ria
AU - Ollila, Hanna M.
AU - Ostrowski, Sisse Rye
AU - Feenstra, Bjarke
N1 - Publisher Copyright:
© The Author(s) 2026.
PY - 2026/2
Y1 - 2026/2
N2 - 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.
AB - 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.
KW - COVID-19/genetics
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Glycosylation
KW - Humans
KW - Membrane Proteins/genetics
KW - Mucin 5AC
KW - Mucin-1/genetics
KW - Polymorphism, Single Nucleotide
KW - SARS-CoV-2/genetics
UR - https://www.scopus.com/pages/publications/105029508245
U2 - 10.1038/s41588-025-02484-9
DO - 10.1038/s41588-025-02484-9
M3 - Journal article
C2 - 41571831
AN - SCOPUS:105029508245
SN - 1061-4036
VL - 58
SP - 299
EP - 306
JO - Nature Genetics
JF - Nature Genetics
IS - 2
ER -