Alternative splicing of OAS1 alters the risk for severe COVID-19

Jennifer Huffman; Guillaume Butler-Laporte; Atlas Khan; Theodore G Drivas; Gina M Peloso; Tomoko Nakanishi; Anurag Verma; Krzysztof Kiryluk; J Brent Richards; Hugo Zeberg

doi:10.1101/2021.03.20.21254005

Alternative splicing of OAS1 alters the risk for severe COVID-19

medRxiv [Preprint]. 2021 Mar 25:2021.03.20.21254005. doi: 10.1101/2021.03.20.21254005.

Authors

Jennifer Huffman¹, Guillaume Butler-Laporte², Atlas Khan³, Theodore G Drivas^{4

5}, Gina M Peloso^{1

6}, Tomoko Nakanishi^{7

8

9

10

11}, Anurag Verma⁴, Krzysztof Kiryluk^{3

12}, J Brent Richards^{2

13}, Hugo Zeberg^{14

15}

Affiliations

¹ Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Bostoon, MA, USA, 02130.
² Departments of Medicine, Human Genetics, Epidemiology, Biostatistics and Occupational Health, McGill University, Lady Davis Institute, Jewish General Hospital, Montréal, Québec, Canada.
³ Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY.
⁴ Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁵ Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia.
⁶ Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118.
⁷ Institute for Molecular Medicine Finland, Univerisity of Helsinki, Helsinki, Finland.
⁸ Department of Human Genetics, McGill University, Montréal, Québec, Canada.
⁹ Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Québec, Canada.
¹⁰ Kyoto-McGill International Collaborative School in Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
¹¹ Research Fellow, Japan Society for the Promotion of Science, Tokyo, Japan.
¹² Institute for Genomic Medicine, Columbia University, New York, NY.
¹³ Department of Twin Research, King's College London, London, UK.
¹⁴ Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany.
¹⁵ Department of Neuroscience, Karolinska Institutet, SE-17177 Stockholm, Sweden.

Abstract

A locus containing OAS1/2/3 has been identified as a risk locus for severe COVID-19 among Europeans ancestry individuals, with a protective haplotype of ∼75 kilobases derived from Neanderthals. Here, we show that among several potentially causal variants at this locus, a splice variant of OAS1 occurs in people of African ancestry independently of the Neanderthal haplotype and confers protection against COVID-19 of a magnitude similar to that seen in individuals without African ancestry.

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