| Title: |
Central role of glycosylation processes in human genetic susceptibility to SARS-CoV-2 infections with Omicron variants |
| Authors: |
Geller, Frank; Wu, Xiaoping; Lammi, Vilma; Abner, Erik; Valliere, Jesse Tyler; Nastou, Katerina; Burns, Angus; Rasmussen, Morten; Andersson, Niklas Worm; Quinn, Liam; Aagaard, Bitten; Banasik, Karina; Bliddal, Sofie; Boding, Lasse; Brunak, Soren; Brons, Nanna; Bybjerg-Grauholm, Jonas; Christoffersen, Lea Arregui Nordahl; Didriksen, Maria; Dinh, Khoa Manh; Erikstrup, Christian; Feldt-Rasmussen, Ulla; Gronbaek, Kirsten; Kaspersen, Kathrine Agergard; Mikkelsen, Christina; Nielsen, Claus Henrik; Nielsen, Henriette Svarre; Nielsen, Susanne Dam; Nissen, Janna; Sequeros, Celia Burgos; Tommerup, Niels; Ullum, Henrik; Spiliopoulos, Lampros; Bager, Peter; Hviid, Anders; Sorensen, Erik; Pedersen, Ole Birger; Lane, Jacqueline M.; Lassauniere, Ria; Ollila, Hanna M.; Ostrowski, Sisse Rye; Feenstra, Bjarke |
| Contributors: |
Institute for Molecular Medicine Finland; Helsinki Institute of Life Science HiLIFE |
| Publisher Information: |
Nature Research |
| Publication Year: |
2026 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
Networks; Insights; Genetics; developmental biology; physiology |
| Description: |
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. ; Peer reviewed |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
We thank all participants and staff related to the Copenhagen Hospital Biobank, Danish Blood Donor Study, EFTER-COVID, FinnGen, EstBB and MGB Biobank for their contribution to this research. This work was supported in full or in part by the National Institutes of Health (NIH) R01AI170850 (J.V.); Novo Nordisk Foundation NNF22OC0077221 and NNF23OC0087269 (S. Bliddal); NordForsk project nos. 105668 and 138929 (L.A.N.C.); NIH R35GM146839 (J.M.L.) and NIH R01HG012810 (J.M.L.); the Academy of Finland no. 353812 (H.M.O.), NIH R01AI170850 (H.M.O.), EU Horizon Europe research and innovation programme 101057553 (H.M.O.) and the Swiss State Secretariat for Education, Research and Innovation, contract number 22.00094 (H.M.O.); and Novo Nordisk Foundation NNF17OC0027594 (B.F.). This work was also supported by research grants from Sygeforsikringen "danmark" 2020-0178 and the EU Horizon REACT study 101057129. The Copenhagen Hospital Biobank was funded by grants from Novo Nordisk Foundation NNF23OC0082015 and Rigshospitalet Research Council (Framework grant) and by Novo Nordisk Foundation CHALLENGE grant NNF17OC0027594. The Danish Blood Donor Study was funded by the Danish Council for Independent Research-Medical Sciences and the Danish Administrative Regions (Bio- and Genome Bank Denmark). The Danish Departments of Clinical Microbiology and Statens Serum Institut carried out laboratory analyses, registration and release of the national SARS-CoV-2 surveillance data for the present study. The work of the Estonian Genome Center, University of Tartu, was funded by the European Union through the Horizon 2020 research and innovation program under grant nos. 894987, 101137201 and 101137154 and Estonian Research Council Grant PRG1291. The Estonian Genome Center analyses were partially carried out in the High Performance Computing Center, University of Tartu. We acknowledge the participants and investigators of the FinnGen study. The FinnGen project is funded by two grants from Business Finland (HUS 4685/31/2016 and UH 4386/31/2016) and the following industry partners: AbbVie, AstraZeneca UK, Biogen MA, Bristol Myers Squibb (and Celgene Corporation & Celgene International II Sarl), Genentech, Merck Sharp & Dohme, Pfizer, GlaxoSmithKline Intellectual Property Development, Sanofi US Services, Maze Therapeutics, Janssen Biotech, Novartis and Boehringer Ingelheim International. The following biobanks are acknowledged for delivering biobank samples to FinnGen: Auria Biobank (www.auria.fi/biopankki), THL Biobank (www.thl.fi/biobank), Helsinki Biobank (www.helsinginbiopankki.fi), Biobank Borealis of Northern Finland (https://www.ppshp.fi/Tutkimus-ja-opetus/Biopankki/Pages/Biobank-Borealis-briefly-in-English.aspx), Finnish Clinical Biobank Tampere (www.tays.fi/en-US/Research_and_development/Finnish_Clinical_Biobank_Tampere), Biobank of Eastern Finland (www.ita-suomenbiopankki.fi/en), Central Finland Biobank (www.ksshp.fi/fi-FI/Potilaalle/Biopankki), Finnish Red Cross Blood Service Biobank (www.veripalvelu.fi/verenluovutus/biopankkitoiminta), Terveystalo Biobank (www.terveystalo.com/fi/Yritystietoa/Terveystalo-Biopankki/Biopankki) and Arctic Biobank (https://www.oulu.fi/en/university/faculties-and-units/faculty-medicine/northern-finland-birth-cohorts-and-arctic-biobank). All Finnish Biobanks are members of BBMRI.fi infrastructure (https://www.bbmri-eric.eu/national-nodes/finland). Finnish Biobank Cooperative-FINBB (https://finbb.fi) is the coordinator of BBMRI-ERIC operations in Finland. The Finnish biobank data can be accessed through the Fingenious services (https://site.fingenious.fi/en) managed by FINBB. We thank the MGB Biobank for providing samples, genomic data and health information data for genetic analyses.; https://hdl.handle.net/10138/628061; 001667216900001 |
| Availability: |
https://hdl.handle.net/10138/628061 |
| Rights: |
cc_by_nc_nd ; info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.2298A22F |
| Database: |
BASE |