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This genetic variant protects against the severity of Covid-19

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An international meta-study led by researchers from the
Karolinska Institutet
has identified a specific genetic variant that protects against severe Covid-19 infection. The researchers were able to identify the variant by studying people of different descent, an achievement they say highlights the importance of conducting clinical trials that include people of diverse backgrounds. The results are published in the journal
«Nature Genetics»
.

In addition to old age and certain underlying diseases, genetics can influence whether we are severely affected or only suffer from mild illness from Covid-19.

Previous studies, conducted primarily on people of European descent, have found that people who carry a particular segment of DNA have a 20% lower risk of developing a serious Covid-19 infection.

However, this region of DNA is packed with numerous genetic variants, making it difficult to unravel the exact protective variant that could serve as a target for medical treatment against severe Covid-19 infection.

The fact that people of African descent had the same protection allowed us to identify the unique variant in the DNA that actually protects from Covid-19 infection.

To identify this specific genetic variant, the researchers identified individuals that carried only parts of that DNA segment. Since Neanderthal heritage occurred after the ancient migration out of Africa, the researchers saw potential in focusing on individuals with african descent that they lack Neanderthal heritage and thus also most of this segment of DNA. However, a small part of this DNA region is the same in people of African and European descent.

Thus they found that people of predominantly African descent had the same protection as those of European descent, which allowed them to identify a specific genetic variant of particular interest.

“The fact that people of African descent had the same protection allowed us to identify the single variant in DNA that actually protects from Covid-19 infection,” says Jennifer Huffman, first author of the study and a researcher at the
VA Boston Healthcare System
(EE.UU).

The analysis included a total of 2,787 hospitalized patients with Covid-19 of African descent Y 130,997 people in a control group from six studies of cohorts. 80% of people of African descent carried the protective variant. The result was compared to a larger earlier meta-study of individuals of European descent.

Key to Covid-19 drug development

According to the researchers, the variant of the protector 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 effective at breaking down SARS-CoV-2, the virus that causes Covid-19 disease.

80% of people of African descent carried the protective variant

“That we are beginning to understand genetic risk factors in detail is key to developing new drugs against Covid-19,” says co-author Brent Richards, principal investigator of the
Lady Davis Institute of the Jewish General Hospital
and professor of
McGill University in Canada
.

The Covid-19 pandemic has stimulated considerable collaboration between researchers from different parts of the world, which has made it possible to study genetic risk factors in a wider variety of individuals than in many previous studies. Even so, the bulk of all clinical research is still being done on people of predominantly European descent.

“This study shows how important it is to include individuals of different ancestors. If we had only studied one group, we would not have been successful in identifying the genetic variant in this case”, concludes research author Hugo Zeberg, from the
Karolinska Institutet.

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