Montreal’s Jewish General helps identify protective gene variant against COVID-19

JGH took part in multinational research collaboration with partners in U.S. and Sweden

An international meta-study conducted by researchers at the Lady Davis Institute of the Jewish General Hospital in Montreal, Karolinska Institutet in Sweden and VA Boston Healthcare System in the U.S. has identified a specific gene variant that protects against severe COVID19 infection. 

The key to understanding 

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

The researchers managed to pinpoint the variant by studying people of different ancestries, a feat they say highlights the importance of conducting clinical trials that include people of diverse descents. 

The role of genetics 

In addition to old age and certain underlying diseases, say the researchers, genetics can influence whether anyone becomes severely affected or only suffers mild illness from COVID-19. Previous studies, mainly on people of European ancestry, found that individuals carrying a particular segment of DNA had a 20 percent lower risk of developing a critical COVID-19 infection. 

From left, study authors Jennifer Huffman from VA Boston Healthcare System, Brent Richards from the Lady Davis Institute of the Jewish General Hospital and McGill University, and Hugo Zeberg from Karolinska Institutet.

According to the research, this DNA segment encodes genes in the immune system and is inherited from Neanderthals in about half of all people outside Africa. 

However, this region of DNA is packed with numerous genetic variants, which makes it challenging to disentangle the exact protective variant that could potentially serve as a target for medical treatment against severe COVID-19 infection. 

Study’s focus on Africans 

So, to identify this specific gene variant, the researchers in the study looked for individuals carrying only parts of this DNA segment. 

Since the Neanderthal inheritance occurred after the ancient migration out of Africa, the researchers saw a potential in focusing on individuals with African ancestry who lack heritage from the Neanderthals and therefore also the majority of this DNA segment. 

The researchers say that a small piece of this DNA region is, however, the same in both people of African and European ancestries. They found that individuals of predominantly African ancestry had the same protection as those of European ancestry, which allowed them to pinpoint a specific gene variant of particular interest. 

Identifying unique variant 

“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 Jennifer Huffman, the first author of the study and a researcher at the VA Boston Healthcare System in the U.S. 

The analysis included a total of 2,787 hospitalized COVID-19 patients of African ancestry and 130,997 people in a control group from six cohort studies. Eighty percent of individuals of African ancestry carried the protective variant. The outcome was compared with a previous, larger meta-study of individuals of European heritage. 

According to the research team, the COVID-19 pandemic has spurred considerable collaboration among researchers in different parts of the world

According to the researchers, the protective gene variant (rs10774671-G) determines the length of the protein encoded by the gene OAS1. Prior studies have shown that the longer variant of the protein is more effective at breaking down SARS-CoV-2, the virus causing the disease COVID-19. 

Pandemic led to collaboration 

According to the research team, the COVID-19 pandemic has spurred considerable collaboration among researchers in different parts of the world. This has made it possible to study genetic risk factors in a wider diversity of individuals than in many previous studies. Even so, they say the majority of all clinical research is still being done on individuals of predominantly European descent. 

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