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.
Highlights
The COVID-19 pandemic has impacted the world for over a year
Several large international efforts[1,2,3,4,5] have been launched to identify the genetic determinants of COVID19 susceptibility and severity. These efforts have identified more than a dozen genomic regions associated with severe COVID-19
When risk haplotypes are long, it is more challenging to disentangle causal genetic variants due to linkage disequilibrium (LD)
Summary
The COVID-19 pandemic has impacted the world for over a year. During this period, several large international efforts[1,2,3,4,5] have been launched to identify the genetic determinants of COVID19 susceptibility and severity. The OAS region was identified as a COVID-19 risk locus in association studies[3,5] of mainly individuals of European ancestry. COVID-19 studies (African ancestry) UKB PMBB CUB BQC-19 VA MVP GenOMICC
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