In addition to old age and certain underlying diseases, genetics can influence whether or not you are severely affected by COVID-19. Previous studies focusing primarily on people of European descent have found that people with a particular segment of DNA have a 20% lower risk of developing a critical form of COVID-19. This segment of DNA codes for immune system genes and is inherited from Neanderthals in about half of people outside Africa.
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| Identification of a protective genetic variant against COVID-19 |
This region of DNA, however, is riddled with numerous genetic variants, making it difficult to disentangle the exact protective variant that could potentially serve as a target for medical treatment against severe COVID-19 infection.
To identify this specific genetic variant, the study researchers looked for individuals who carried only certain parts of this DNA segment. Since Neanderthal heritage occurred after the ancient migration out of Africa, researchers have focused on individuals of African descent who lack Neanderthal heritage and therefore also the majority of this DNA segment. A small piece of this region of DNA, however, is the same in people of African and European descent.
The researchers found that people of predominantly African ancestry enjoyed the same protection as those of European ancestry, which allowed them to identify a specific genetic variant of particular interest.
"The fact that individuals of African descent had the same protection allowed us to identify the single DNA variant that actually protects against COVID-19 infection," says Jennifer Huffman, lead author of the study and researcher at the VA Boston Healthcare System in the United States.
The analysis included a total of 2,787 hospitalized patients with COVID-19 and African descent, as well as 130,997 people in a control group, from six cohort studies. Eighty percent of people of African descent carried the protective variant. The results were compared with those of a previous larger meta-study in people of European descent.
According to the researchers, the protective variant of the gene (rs10774671-G) determines the length of the protein encoded by the OAS1 gene. Previous studies have shown that the longer variant of the protein is more efficient at breaking down SARS-CoV-2, the virus that causes COVID-19.
"The fact that we are beginning to understand genetic risk factors in detail is critical for the development of new drugs for COVID-19," says co-author Brent Richards, a senior researcher at the Hospital's Lady Davis Institute. Jewish general and professor at McGill University in Canada.
The COVID-19 pandemic has prompted considerable collaboration between researchers from different parts of the world, which has allowed the study of genetic risk factors in a greater diversity of individuals than in many previous studies. Despite this, the majority of clinical research is still done on people of European descent.
"This study shows how important it is to include individuals from different ethnic backgrounds. If we had only studied one group, we would not have been able to identify this specific genetic variant," says the The study's lead author, Hugo Zeberg, an assistant professor in the department of neuroscience at Karolinska Institutet.
Publication:
Jennifer E. Huffman, Guillaume Butler-Laporte, Atlas Khan, Erola Pairo-Castineira, Theodore G. Drivas, Gina M. Peloso, Tomoko Nakanishi, COVID-19 Host Genetics Initiative, Andrea Ganna, Anurag Verma, J. Kenneth Baillie, Krzysztof Kiryluk, J. Brent Richards and Hugo Zeberg. Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19. Nat Genet (2022), doi: 10.1038/s41588-021-00996-8.
Contact:
Pascal Fischer - Research Communications and External Relations Officer - pascal.fischer at ladydavis.ca
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