{"id":395,"date":"2022-10-18T15:58:00","date_gmt":"2022-10-18T15:58:00","guid":{"rendered":"https:\/\/boulantlab.com\/?post_type=publications&#038;p=395"},"modified":"2022-10-26T16:01:54","modified_gmt":"2022-10-26T16:01:54","slug":"genetic-regulation-of-oas1-nonsense-mediated-decay-underlies-association-with-covid-19-hospitalization-in-patients-of-european-and-african-ancestries","status":"publish","type":"publications","link":"https:\/\/boulantlab.com\/publications\/genetic-regulation-of-oas1-nonsense-mediated-decay-underlies-association-with-covid-19-hospitalization-in-patients-of-european-and-african-ancestries\/","title":{"rendered":"Genetic regulation of OAS1 nonsense-mediated decay underlies association with COVID-19 hospitalization in patients of European and African ancestries"},"content":{"rendered":"\n<p>The chr12q24.13 locus encoding OAS1-OAS3 antiviral proteins has been associated with coronavirus disease 2019 (COVID-19) susceptibility. Here, we report genetic, functional and clinical insights into this locus in relation to COVID-19 severity. In our analysis of patients of European (n = 2,249) and African (n = 835) ancestries with hospitalized versus nonhospitalized COVID-19, the risk of hospitalized disease was associated with a common OAS1 haplotype, which was also associated with reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in a clinical trial with pegIFN-\u03bb1. Bioinformatic analyses and in vitro studies reveal the functional contribution of two associated OAS1 exonic variants comprising the risk haplotype. Derived human-specific alleles rs10774671-A and rs1131454 -A decrease OAS1 protein abundance through allele-specific regulation of splicing and nonsense-mediated decay (NMD). We conclude that decreased OAS1 expression due to a common haplotype contributes to COVID-19 severity. Our results provide insight into molecular mechanisms through which early treatment with interferons could accelerate SARS-CoV-2 clearance and mitigate against severe COVID-19.<\/p>\n","protected":false},"featured_media":396,"template":"","_links":{"self":[{"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/publications\/395"}],"collection":[{"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/publications"}],"about":[{"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/types\/publications"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/media\/396"}],"wp:attachment":[{"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/media?parent=395"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}