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<p>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 <i>ST6GAL1</i>, a gene affecting immune development and function, connected to three other associated loci (harboring <i>MUC1</i>, <i>MUC5AC</i> and <i>MUC16</i>) 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.</p>

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Central role of glycosylation processes in human genetic susceptibility to SARS-CoV-2 infections with Omicron variants

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月22日

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  • Frank Geller,
  • Xiaoping Wu,
  • Vilma Lammi,
  • Erik Abner,
  • Jesse Tyler Valliere,
  • Katerina Nastou,
  • Angus Burns,
  • Morten Rasmussen,
  • Niklas Worm Andersson,
  • Liam Quinn,
  • Bitten Aagaard,
  • Karina Banasik,
  • Sofie Bliddal,
  • Lasse Boding,
  • Søren Brunak,
  • Nanna Brøns,
  • Jonas Bybjerg-Grauholm,
  • Lea Arregui Nordahl Christoffersen,
  • Maria Didriksen,
  • Khoa Manh Dinh,
  • Christian Erikstrup,
  • Ulla Feldt-Rasmussen,
  • Kirsten Grønbæk,
  • Kathrine Agergård Kaspersen,
  • Christina Mikkelsen,
  • Claus Henrik Nielsen,
  • Henriette Svarre Nielsen,
  • Susanne Dam Nielsen,
  • Janna Nissen,
  • Celia Burgos Sequeros,
  • Niels Tommerup,
  • Henrik Ullum,
  • Lampros Spiliopoulos,
  • Peter Bager,
  • Anders Hviid,
  • Erik Sørensen,
  • Ole Birger Pedersen,
  • Jacqueline M. Lane,
  • Ria Lassaunière,
  • Hanna M. Ollila,
  • Sisse Rye Ostrowski,
  • Bjarke Feenstra

摘要

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.