Genetic risk factors for severe COVID-19 identified

In March 2020, thousands of researchers across the globe joined forces to answer the question of why some COVID-19 patients develop a severe, life-threatening disease, while others manage with mild or no symptoms. A comprehensive summary of their findings to date, based on the analyses of nearly 50,000 patients and published in Nature today, reveals 13 genetic regions that are strongly associated with infection or severe COVID-19.

Why do some people get severely ill from COVID-19? In addition to risk factors such as age and diabetes, some of this is attributable to our varying genetic makeup and susceptibility to severe illness from COVID-19. A large sampling of patients is required for identifying such genetic risk factors. Consequently, the global COVID-19 Host Genetics Initiative was launched at the onset of the pandemic. The initiative currently encompasses more than 61 studies from 25 countries. Researchers from Karolinska Institutet and Uppsala University were incorporated through the Swedish SweCovid study of the genetic data of approximately 300 individuals who had been hospitalised with intensive care.

13 genetic regions

Portrait photo of Hugo Zeberg, researcher at the Department of Neuroscience, Karolinska Institutet, and Max Planck Institute for Evolutionary Anthropology.
Hugo Zeberg. Photo: private

"The results of this largescale international collaboration indicate the robustness of utilising genetic studies to learn more about infectious diseases. We can use genetics to better understand COVID-19," explains Hugo Zeberg, researcher at the Department of Neuroscience, Karolinska Institutet, and Head of Swedish contributions to the project.

Researchers have identified 13 genetic regions that are strongly associated with SARS-CoV-2 infection or severe COVID-19. The next step is to understand why the identified genetic variations cause severe illness. Among the newly identified risk factors are genetic variations already known to be linked to lung cancer, and autoimmune and inflammatory diseases, as well as genetic variations that are crucial to our defences against infectious diseases.

May lead to new treatments

"The genetic discoveries provide us with vital knowledge that paves the way for the development of new treatments for patients with severe COVID-19," explains Michael Hultström, physician and researcher at Uppsala University, who worked with the collection of genetic data from Swedish patients.

Two of the genetic risk factors were more prevalent among patients of East Asian or South Asian ancestry than among patients of European ancestry, highlighting the importance of collecting genetic data from various regions of the world. The pandemic has resulted in extensive collaborations between researchers throughout the world, which has enabled the largescale genetic analyses.

"This only illustrates just how much better science is - how much faster it goes and how much more we discover - when we work together," said Andrea Ganna, researcher at the University of Helsinki and founder of the COVID-19 Host Genetics Initiative.

The analyses also indicate the probability of a causal link between factors such as smoking and a high BMI (body mass index), and the risk of developing severe COVID-19.

Publication

"Mapping the human genetic architecture of COVID-19". The COVID-19 Host Genetics Initiative (Andrea Ganna et al), Nature, online 8 July 2021, doi: 10.1038/s41586-021-03767-x.

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