Abstract
The OAS1/2/3 cluster has been identified as a risk locus for severe COVID-19 among individuals of European ancestry, with a protective haplotype of approximately 75 kilobases (kb) derived from Neanderthals in the chromosomal region 12q24.13. This haplotype contains a splice variant of OAS1, which occurs in people of African ancestry independently of gene flow from Neanderthals. Using trans-ancestry fine-mapping approaches in 20,779 hospitalized cases, we demonstrate that this splice variant is likely to be the SNP responsible for the association at this locus, thus strongly implicating OAS1 as an effector gene influencing COVID-19 severity.
Original language | English |
---|---|
Pages (from-to) | 125-127 |
Number of pages | 3 |
Journal | Nature Genetics |
Volume | 54 |
Issue number | 2 |
DOIs | |
Publication status | Published - Feb 2022 |
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In: Nature Genetics, Vol. 54, No. 2, 02.2022, p. 125-127.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19
AU - COVID-19 Host Genetics Initiative
AU - Huffman, Jennifer E
AU - Butler-Laporte, Guillaume
AU - Khan, Atlas
AU - Pairo-Castineira, Erola
AU - Drivas, Theodore G
AU - Peloso, Gina M
AU - Nakanishi, Tomoko
AU - Ganna, Andrea
AU - Verma, Anurag
AU - Baillie, J Kenneth
AU - Kiryluk, Krzysztof
AU - Richards, J Brent
AU - Zeberg, Hugo
AU - van de Beek, Diederik
N1 - Funding Information: We thank the COVID-19 Host Genetics Initiative and Regeneron for making the data from the genome-wide association study available. Genotyping and phenotyping of the Columbia University cohort was made possible by the Columbia University COVID-19 Biobank Genomics Workgroup members, including R. Mayeux, M. P. Reilly, W. Chung, D. B. Goldstein, C. K. Garcia, I. Ionita-Laza, A. Califano, S. M. O’Byrne, D. Pendrick, S. Sengupta, P. Sims and A.-C. Uhlemann. The Columbia University COVID-19 Biobank was supported by Columbia University and the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), through grant no. UL1TR001873. A.K. was supported by grant no. K25(K25DK128563) from the NIH/National Institute of Diabetes and Digestive and Kidney Diseases and grant no. TL1(UL1TR001873) from NIH/NCATS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The Richards research group is supported by the Canadian Institutes of Health Research (CIHR) (grant nos. 365825 and 409511), the Lady Davis Institute of the Jewish General Hospital, the Canadian Foundation for Innovation, the NIH Foundation, Cancer Research UK, Genome Québec, the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche du Québec Santé (FRQS). G.B.-L. is supported by a CIHR scholarship and a joint FRQS and Québec Ministry of Health and Social Services scholarship. T.N. is supported by a research fellowship of the Japan Society for the Promotion of Science for Young Scientists. J.B.R. is supported by an FRQS Clinical Research Scholarship. We acknowledge support from Calcul Québec and Compute Canada. TwinsUK is funded by the Wellcome Trust, the Medical Research Council, the European Union, the National Institute for Health Research-funded BioResource and the Clinical Research Facility and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London. The Biobanque Québec COVID-19 is funded by FRQS, Genome Québec and the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in Infection and Immunity and FRQS. GenOMICC controls were obtained using UK Biobank Resource under project 788 funded by Roslin Institute Strategic Programme Grants from the BBSRC (BBS/E/D/10002070 and BBS/E/D/30002275) and Health Data Research UK (references HDR-9004 and HDR-9003). The PMBB is funded by a gift from the Smilow family, the NCATS of the NIH under Clinical and Translational Science Award no. UL1TR001878 and the Perelman School of Medicine at the University of Pennsylvania. H.Z. is supported by the Jeanssons and Magnus Bergsvalls Foundations the Swedish Research Council (2021-03050). We thank the PMBB team members who made this work possible, including D. Rader, M. Ritchie, Y. Bradford, S. Setia Verma, A. Lucas and B. Li. We thank S. Pääbo for careful reading of the manuscript and helpful comments. The funding agencies had no role in the design, implementation or interpretation of this study. Funding Information: J.B.R. has served as an advisor to GlaxoSmithKline and Deerfield Capital. His institution has received investigator-initiated grant funding from Eli Lilly, GlaxoSmithKline and Biogen for projects unrelated to this research. He is the founder of 5 Prime Sciences. The other authors declare no competing interests. Publisher Copyright: © 2022, The Author(s).
PY - 2022/2
Y1 - 2022/2
N2 - The OAS1/2/3 cluster has been identified as a risk locus for severe COVID-19 among individuals of European ancestry, with a protective haplotype of approximately 75 kilobases (kb) derived from Neanderthals in the chromosomal region 12q24.13. This haplotype contains a splice variant of OAS1, which occurs in people of African ancestry independently of gene flow from Neanderthals. Using trans-ancestry fine-mapping approaches in 20,779 hospitalized cases, we demonstrate that this splice variant is likely to be the SNP responsible for the association at this locus, thus strongly implicating OAS1 as an effector gene influencing COVID-19 severity.
AB - The OAS1/2/3 cluster has been identified as a risk locus for severe COVID-19 among individuals of European ancestry, with a protective haplotype of approximately 75 kilobases (kb) derived from Neanderthals in the chromosomal region 12q24.13. This haplotype contains a splice variant of OAS1, which occurs in people of African ancestry independently of gene flow from Neanderthals. Using trans-ancestry fine-mapping approaches in 20,779 hospitalized cases, we demonstrate that this splice variant is likely to be the SNP responsible for the association at this locus, thus strongly implicating OAS1 as an effector gene influencing COVID-19 severity.
UR - http://www.scopus.com/inward/record.url?scp=85122848890&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41588-021-00996-8
DO - https://doi.org/10.1038/s41588-021-00996-8
M3 - Article
C2 - 35027740
SN - 1061-4036
VL - 54
SP - 125
EP - 127
JO - Nature Genetics
JF - Nature Genetics
IS - 2
ER -