A global network of researchers presents their conclusions on the genetic risk to Covid-19. The consortium of scientists COVID-19 Host Genetics Initiative has identified 13 genetic regions associated with the susceptibility and severity of SARS-CoV-2 infection. Some of these areas are in turn related to inflammatory or autoimmune diseases, and lung diseases.
The macro-analysis has counted about 50,000 patients affected by covid. These had been included in 46 studies conducted in nearly twenty countries, making it the largest genome-wide association study to date. Its fruits will help develop treatments for the disease.
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“In this type of study, all the genes are analyzed and those that are associated with the pathology examined come to light. They are, therefore, unbiased studies that are approached without any preconceived ideas, which makes them very robust. In this particular one, we have been able to confirm results that had been previously achieved ”, says in a telephone interview Israel Fernández, head of the Pharmacogenomics and Neurovascular Genetics group at the Research Institute of Sant Pau Hospital (Barcelona) and a member of the consortium.
At the start of the pandemic, in March 2020, the COVID-19 Host Genetics Initiative (COVID-19 HGI) was created. This global consortium of researchers focused on understanding the role of genes in SARS-CoV-2 disease. “The idea was to find what metabolic pathways, what processes were related to the severity of the covid,” says Fernández.
COVID-19 Host Genetics Initiative
Currently, more than 3,000 scientists participate in the project with 61 studies in 25 countries
The initiative generated a shared network of data and results to analyze the genetic component in this complex disease. Even private genomics companies have joined the project in which more than 3,000 scientists are currently participating with 61 studies in 25 countries.
The meta-analysis of the conclusions obtained during this long year of work is presented this Thursday in the journal Nature. It is the fifth data analysis carried out throughout said period, which can be consulted at the project website.
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The 13 genetic regions identified were found throughout the entire genome. Some of these genes are common to other pathologies that are central to coronavirus disease, such as lung conditions or inflammation.
One of them is FOXP4, which is related to lung cancer and inflammation in the area. The variant for this gene that was associated with severe covid increased its expression. This was found much more frequently in Asian or Hispanic populations. A possible treatment would therefore be aimed at inhibiting the expression of FOXP4.
The DPP9 gene, also implicated in lung cancer and pulmonary fibrosis, appeared to be associated with a severe course of the disease. Others, such as TYK2, are themselves implicated in some autoimmune diseases.
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“It was already known that there were certain associated genetic factors, but we are seeing that there are many processes related to the immune and inflammatory systems that intervene both in the risk of infection and in having serious symptoms”, says Fernández.
A greater susceptibility to infection was linked to the ABO group, which determines the blood type. Previous studies had already shown similar results, although they also pointed to a certain relationship with the severity of the covid.
Like covid
In complex diseases, there are thousands of genetic variables and all together increase the risk of greater severity
The genes involved pose a low risk when considered individually, but collectively they are of greater significance.
“In complex diseases like covid, there are thousands of genetic variables and all together increase the risk of greater severity. It’s like the lottery: the more tickets you have, the more options you will have to win the prize, ”says Fernández.
Other risk factors such as sex, age or obesity would also be added to the genes. Regarding the first, in the analysis published today no differences were found in relation to genetic influence. On the other hand, a greater predisposition to suffer from severe covid was seen in relation to being overweight.
The inclusion of different populations appears as one of the strengths of the study thanks to its vast number of participants – to the 50,000 covid patients we must add two million healthy people in the control groups. However, despite the authors’ efforts to include genetically diverse study groups, about 80% of the participants are of European descent.
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The next results will come from a sample of 125,000 patients with SARS-CoV-2 infection that is already being analyzed. The researchers expect an increase in the new regions associated with severe cases of covid by having a much larger number of participants. The interest is especially focused on las variants for the ACE2 receptor through which the virus infects cells and the SFTPD gene, involved in the response to respiratory pathogens in the lung.
Ongoing research can provide new insights into how infection causes disease and thus identify targets for future drugs to target.
Also for the repositioning of these. Knowing the biological pathways that you want to modify to treat a disease allows you to test a drug already on the market that acts in those same pathways. Thus, it is possible to work faster for the development of treatments.
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