A large genomic analysis reveals the risk factors for COVID-19

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Novell Coronavirus SARS-CoV-2 Transmission electron micrograph of SARS-CoV-2 virus particles, isolated from a patient. Image captured and enhanced in color at NIAID’s Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: National Institute of Allergies and Infectious Diseases, NIH

In March 2020, thousands of scientists around the world came together to answer an urgent and complex question: what genetic factors influence some patients with COVID-19 to develop serious, life-threatening diseases that require hospitalization, while that others escape with mild symptoms or none?

An exhaustive summary of his findings so far published in Nature, reveals 13 loci or locations in the , which are strongly associated with severe COVID-19 infections. The researchers also identified causal factors such as smoking and high body mass index. These results come from one of the largest genome-wide association studies ever conducted, which includes nearly 50,000 patients with COVID-19 and two million uninfected controls.

The results could help provide goals for future therapies and illustrate the power of genetic studies in learning more about infectious diseases.

This global effort, called the COVID-19 Host Genomics Initiative, was founded in March 2020 by Andrea Ganna, group leader at the Institute of Molecular Medicine of Finland (FIMM), University of Helsinki, and Mark Daly, director of FIMM and member of the institute at the Broad Institute of MIT and Harvard. The initiative has become one of the most extensive collaborations in human genetics and currently includes more than 3,300 authors and 61 studies from 25 countries.

Ben Neale, co-director of the study’s Medical and Population Genetics Program and lead co-author of the study, said that while vaccines provide protection against infection, there is still substantial room for improvement in COVID treatment. -19, which can be reported by . He added that improving treatment methods could help shift the pandemic, which has required major shutdowns in much of the world, to a more localized endemic disease that is present at low but consistent levels in the population, as is the flu. .

“The better we treat COVID-19, the better equipped the medical community could be to control the disease,” he said. “If we had a mechanism to treat the infection and get someone out of the hospital, that would radically alter our response to public health.”

Take advantage of diversity

To make their analysis, the consortium grouped clinic and of the nearly 50,000 patients in his study who tested positive for the virus and 2 million controls at numerous biobanks, clinical trials, and direct consumer genetic companies such as 23andMe. Due to the large amount of data included worldwide, scientists were able to produce statistically robust analyzes much more quickly and from a greater diversity of populations, than any group could have on its own.

Of the 13 loci identified so far by the team, two had higher frequencies among patients of East Asian or South Asian descent than those of European descent, emphasizing the importance of diversity in genetic data sets. .

“We have been much more successful than previous efforts in sampling genetic diversity because we have made a concerted effort to reach populations around the world,” Daly said. “I think we still have a long way to go, but we’re moving very well.”

The team highlighted one of these two loci in particular, close to the FOXP4 gene, which is linked to lung cancer. The FOVP4 variant associated with severe COVID-19 increases gene expression, suggesting that inhibiting the gene could be a potential therapeutic strategy. Other loci associated with severe COVID-19 included DPP9, a gene also implicated in lung cancer and lung fibrosis, and TYK2, which is involved in some autoimmune diseases.

Mari Niemi, also of FIMM and lead analyst of the study, says the consortium gave priority to communication as scientists analyzed the data, immediately posting the results on its website after checking their accuracy. . The team hopes its results can point to useful targets for reused drugs.

Researchers will continue to study more data as they enter and update their results using the “Matters Arising” format at Nature. They will begin to study what differentiates “long-haul carriers,” or patients the symptoms of COVID-19 persist for months, from others, and will continue to identify additional loci associated with serious infections and diseases.

“We would like to try to get a good handful of very specific therapeutic hypotheses next year,” Daly said. “Really, we are likely to treat COVID-19 as a serious health problem for a long time. Any therapist that arises this year, for example, from the reuse of an existing drug based on clear genetic knowledge, would have a great impact “.

A new space for genetics

Ganna stressed that scientists were able to find robust genetic signals because of their collaborative efforts, a cohesive spirit of data sharing and transparency, and the urgency of knowing the entire world facing the same threat at the same time. He added that geneticists, who regularly work with large data sets, know the benefits of open collaboration for a long time. “This just illustrates the improvement of science, the speed at which it goes and the amount more we discover, when we work together,” Ganna said.

Daly, meanwhile, is thrilled with the clarity and interpretation of his results for geneticists. He says the ideas in this work have been unique and may change the paradigm for the field of , which has been dominated by studies of common chronic diseases, rare genetic diseases, and cancer.

“These findings have been really informative and this has led us to realize that there is great untapped potential in the use of genetics to understand and develop potentially therapeutic for infectious diseases,” Daly said. “I hope this is an example of how we could contribute it addresses a new set of issues that are especially important in the developing parts of the world. ”


Genes and sleep apnea associated with risk of severe COVID-19


More information:
The host genetics initiative COVID-19. Mapping of human genetic architecture of COVID-19. Nature. Online July 8, 2021. DOI: 10.1038 / s41586-021-03767-x , www.nature.com/articles/s41586-021-03767-x

Citation: Large genomic analysis reveals risk factors COVID-19 (2021, July 8) retrieved July 8, 2021 at https://medicalxpress.com/news/2021-07-large-genomic -analysis-highlights-covid-.html

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