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More gene variants that influence severity of COVID-19 identified

24 January 2022
Appeared in BioNews 1129

Gene variants that decrease and increase the risk of severe COVID-19 infection, respectively, have been identified in separate studies.

Using data from clinical trials that include people of diverse descents, the first study, an international metastudy, has led to the discovery of the specific genetic variant of the OAS1 gene that is known to significantly reduce the risk of developing severe COVID-19.

'This study shows how important it is to include people of different ancestries. If we had only studied one group, we would not have been successful in identifying the gene variant in this case,' said Dr Hugo Zeberg, assistant professor at the Department of Neuroscience at Karolinska Institutet, Sweden, and corresponding author of the study.

Dr Zeberg had previously discovered that a region on chromosome 12 that reduces the risk of severe COVID-19 by 20 percent is inherited from Neanderthals, which half of all people outside Africa carry (see BioNews 1084). The genes in this region are called OAS and are responsible for the synthesis of a protein produced within the immune system that destroys viral particles. The OAS1 gene has previously been implicated to affect the severity of SARS-CoV-2 infection (see BioNews 1115).

The large-scale study, published in Nature Genetics, analysed the genetic profiles of 2787 patients with COVID-19 of African heritage and 130,997 genetic profiles of controls also of African ancestry recorded in six other cohort studies, acting as a control population.

Focusing on people with African ancestry who did not inherit genes from the Neanderthals due to migration, the scientists discovered that a small segment of DNA was the same in both people of African and European descent. This small segment offered the same protection against severe COVID-19 and allowed the scientists to pinpoint the specific gene variant (rs10774671-G), which 80 percent of people of African descent carried.

'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' said Dr Jennifer Huffman, lead author of the study and researcher at VA Boston Healthcare System, Massachusetts.

This study highlights the importance of sampling the genomes of a diverse cross-section of society.

In contrast, a separate unpublished study has identified a genetic variant that more than doubles the risk of developing severe COVID-19.

Scientists at the Medical University of Bialystok, Poland analysed the genomes of 1500 COVID-19 patients in Poland to isolate the variant. Located on chromosome 3, it is estimated that 14 percent of Poles have the variant, compared to 9 percent within the general European population. Poland has higher than average COVID-19 deaths compared to many other European nations and the scientists have identified this variant as the fourth most important factor in determining a person's reaction to COVID-19 infection behind age, weight, and gender.

'After more than a year and a half of work it was possible to identify a gene responsible for a predisposition to becoming seriously ill (with coronavirus).' said Adam Niedzielski, Poland's health minister. 'This means that in the future we will be able to… identify people with a predisposition to suffer seriously from COVID.'

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