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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.

SUBMITTER: Huffman JE

PROVIDER: S-EPMC8837537 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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

Huffman Jennifer E JE Butler-Laporte Guillaume G Khan Atlas A Pairo-Castineira Erola E Drivas Theodore G TG Peloso Gina M GM Nakanishi Tomoko T Ganna Andrea A Verma Anurag A Baillie J Kenneth JK Kiryluk Krzysztof K Richards J Brent JB Zeberg Hugo H

Nature genetics 20220113 2

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 l ...[more]

PMID: 35027740

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