Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19

COVID-19 Host Genetics Initiative

doi:10.1038/s41588-021-00996-8

Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19

COVID-19 Host Genetics Initiative

Research output: Contribution to journal › Article › peer-review

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
Journal	Nature Genetics
Volume	54
Issue number	2
Early online date	13 Jan 2022
DOIs	https://doi.org/10.1038/s41588-021-00996-8
Publication status	Published - Feb 2022

Keywords

2',5'-Oligoadenylate Synthetase/genetics
Blacks/genetics
COVID-19/enzymology
Genetic Predisposition to Disease
Humans
Linkage Disequilibrium/genetics
Physical Chromosome Mapping
RNA Splicing/genetics
Risk Factors
Severity of Illness Index
Whites/genetics

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s41588-021-00996-8Final published version, 2.52 MBLicence: Creative Commons: Attribution (CC-BY)

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title = "Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19",

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.",

keywords = "2',5'-Oligoadenylate Synthetase/genetics, Blacks/genetics, COVID-19/enzymology, Genetic Predisposition to Disease, Humans, Linkage Disequilibrium/genetics, Physical Chromosome Mapping, RNA Splicing/genetics, Risk Factors, Severity of Illness Index, Whites/genetics",

author = "{COVID-19 Host Genetics Initiative} and Huffman, {Jennifer E} and Guillaume Butler-Laporte and Atlas Khan and Erola Pairo-Castineira and Drivas, {Theodore G} and Peloso, {Gina M} and Tomoko Nakanishi and Andrea Ganna and Anurag Verma and Baillie, {J Kenneth} and Krzysztof Kiryluk and Richards, {J Brent} and Hugo Zeberg",

note = "{\textcopyright} 2022. The Author(s).",

year = "2022",

month = feb,

doi = "10.1038/s41588-021-00996-8",

language = "English",

volume = "54",

pages = "125--127",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "2",

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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

PY - 2022/2

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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.

KW - 2',5'-Oligoadenylate Synthetase/genetics

KW - Blacks/genetics

KW - COVID-19/enzymology

KW - Genetic Predisposition to Disease

KW - Humans

KW - Linkage Disequilibrium/genetics

KW - Physical Chromosome Mapping

KW - RNA Splicing/genetics

KW - Risk Factors

KW - Severity of Illness Index

KW - Whites/genetics

U2 - 10.1038/s41588-021-00996-8

DO - 10.1038/s41588-021-00996-8

M3 - Article

C2 - 35027740

VL - 54

SP - 125

EP - 127

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 2

ER -

Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19

Abstract

Keywords

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