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.
【저자키워드】 Infectious diseases, Immunogenetics, Genetic association study, 【초록키워드】 Hospitalized, severe COVID-19, OAS1, variant, COVID-19 severity, risk, African, Cluster, SNP, Protective, Haplotype, association, gene flow, locus, individual, Neanderthal, chromosomal region, European, responsible, approach, occur, splice, splice site, 【제목키워드】 risk,