NEW YORK (Reuters Health) - Researchers have identified a human genetic variant that appears to protect against severe COVID-19 infection, and which could serve as a target for drug development.
Earlier work identified the OAS1/2/3 gene cluster as a risk locus for severe COVID-19 among mainly individuals of European ancestry. The protective haplotype contains an alternative-splice variant of OAS1 (rs10774671).
To test the association of this splice variant with COVID-19 outcomes in people of African ancestry, the researchers analyzed genetic data on 2,787 hospitalized COVID-19 patients and 130,997 controls of African ancestry.
They found the splice variant conferred protection against COVID-19 hospitalization in individuals of African ancestry, in line with the protection seen previously in Europeans.
"The fact that individuals of African descent had the same protection allowed us to identify the unique variant in the DNA that actually protects from COVID-19 infection," Dr. Jennifer Huffman, first author of the study in Nature Genetics and a researcher at the VA Boston Healthcare System, said in a news release.
"That we are beginning to understand the genetic risk factors in detail is key to developing new drugs against COVID-19," added co-author Dr. Brent Richards with the Lady Davis Institute of the Jewish General Hospital and professor at McGill University in Canada.
"This study shows how important it is to include individuals of different ancestries. If we had only studied one group, we would not have been successful in identifying the gene variant in this case," added corresponding author Dr. Hugo Zeberg of Karolinska Institutet, in Stockholm, Sweden.
In their report, the authors note that the "OAS genes encode enzymes catalyzing the synthesis of short polyadenylates, which activate ribonuclease L that in turn degrades intracellular double-stranded RNA and triggers several other antiviral mechanisms." According to previous research, the protective haplotype confers approximately 23% reduced risk of becoming critically ill on infection with SARS-CoV-2, they add.
SOURCE: https://go.nature.com/3Isz0mB Nature Genetics, online January 13, 2022.
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