期刊
NATURE GENETICS
卷 54, 期 2, 页码 125-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41588-021-00996-8
关键词
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资金
- Columbia University
- National Center for Advancing Translational Sciences (NCATS)
- National Institutes of Health (NIH) [UL1TR001873]
- NIH/National Institute of Diabetes and Digestive and Kidney Diseases [K25(K25DK128563)]
- NIH/NCATS [TL1(UL1TR001873)]
- Canadian Institutes of Health Research (CIHR) [365825, 409511]
- Lady Davis Institute of the Jewish General Hospital
- Canadian Foundation for Innovation
- NIH Foundation
- Cancer Research UK
- Genome Quebec
- Public Health Agency of Canada
- McGill Interdisciplinary Initiative in Infection and Immunity
- Fonds de Recherche du Quebec Sante (FRQS)
- CIHR scholarship
- FRQS
- Quebec Ministry of Health and Social Services scholarship
- Japan Society for the Promotion of Science for Young Scientists
- FRQS Clinical Research Scholarship
- Calcul Quebec and Compute Canada
- Wellcome Trust
- Medical Research Council
- European Union
- National Institute for Health Research-funded BioResource
- Clinical Research Facility and Biomedical Research Centre based at Guy's and St. Thomas' NHS Foundation Trust in partnership
- King's College London
- Roslin Institute Strategic Programme Grants from the BBSRC [BBS/E/D/10002070, BBS/E/D/30002275, 778]
- Health Data Research UK [HDR-9004, HDR-9003]
- NCATS of the NIH under Clinical and Translational Science [UL1TR001878]
- Jeanssons and Magnus Bergsvalls Foundations the Swedish Research Council [2021-03050]
- Swedish Research Council [2021-03050] Funding Source: Swedish Research Council
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 derived from Neanderthals. The splice variant of OAS1 is found in individuals of African ancestry independently, and it is likely responsible for the association with COVID-19 severity.
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. Multi-ancestry fine-mapping of the OAS1/2/3 region shows that a splice site variant in OAS1 is likely responsible for the association of this locus with the risk of severe COVID-19.
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