Large-scale genomic analysis indicates COVID-19 risk factors.
International collaboration has uncovered several genetic markers associated with SARS-CoV-2 infection and COVID-19 severity.
In March 2020, thousands of scientists from around the globe came together to answer an urgent yet very complex question: what genetic factors could affect the fact that some COVID-19 patients develop a severe, life-threatening illness requiring hospitalisation, while others experience only mild symptoms or no symptoms at all?
A comprehensive summary of their current findings, which was published in a prestigious scientific journal Nature, indicates 13 loci, or locations in the human genome that are strongly associated with infection or severe course of COVID-19. The researchers also identified such causal factors as smoking and high body mass index (BMI). These results come from one of the largest genome-wide association studies (GWAS) ever conducted, involving nearly 50,000 COVID-19 patients and two million non-infected controls in the study.
This global effort, called COVID-19 Host Genomics Initiative (HGI), was founded in March 2020 by Andrea Ganna, a research team leader in Finnish Institute of Molecular Medicine (FIMM), University of Helsinki and Mark Daly , a director of FIMM and an employee of the Broad Institute of MIT and Harvard. The initiative has grown into one of the most extensive collaborations in human genetics, involving 61 projects from 25 countries.
Exploiting diversity
Due to the large amount of data coming in from around the world, researchers were able to perform high statistical power analyses much more quickly based on a greater diversity of population than any single group could do on its own.
Out of the 13 loci identified by the team so far, two had a higher incidence in patients of East Asian or South Asian origin than in patients of European origin. "We have been much more successful than previous attempts to collect genetic diversity, because we have made a concerted effort to reach populations around the world," – said Daly. The team paid special attention to one of these two loci, near the gene FOXP4 which is associated with lung cancer. Variant FOXP4 associated with a severe course of COVID-19 increases gene expression, suggesting that gene inhibition may be a potential therapeutic strategy. Other loci associated with the severe course of COVID-19 include DPP9, a gene also implicated in lung cancer and pulmonary fibrosis, and TYK2 which is associated with some autoimmune diseases.
"The mentioned article is the work of more than 3,500 co-authors from over 1,200 scientific and clinical units from around the world, which demonstrates the enormous scale of the whole project. It was necessary to efficiently organise the entire HGI consortium in the aspect of substantive supervision of partner projects, administration, information flow between members and the provision of direct communication channels and administration of sent genomic data and the current release of the results of meta-analyses” - said Karolina Chwiałkowska, PhD, co-author of the publication, researcher from the Centre for Bioinformatics and Data Analysis of the Medical University of Bialystok. Karolina Chwiałkowska, PhD was involved in supporting the management of the consortium COVID-19 Host Genomics initiative from the first months of its existence. She worked closely with project leaders from the Broad Institute (MIT & Harvard, MA, USA) and FIMM (Finland). It is also worth noting that among the co-authors is another MUB employee, Alexander Teumer from the Department of Population Medicine and Lifestyle Diseases Prevention headed by Prof. Karol Kamiński.
It is worth noting that two independent projects from Poland will be included in the work of the HGI consortium, the results of which are currently being prepared for a publication: “POLCOVID-Genomics” (leader: Medical University of Bialystok, technology partner: biotechnological company IMAGENE.ME ) and "Search for genomic markers predicting the severity of the response to COVID-19” (Central Clinical Hospital of the Ministry of Interior and Administration in Warsaw, MNM diagnostics, Józef Struś General City Hospital).
As part of the project “POLCOVID-Genomics” , which is headed by Prof. Marcin Moniuszko, PhD, MD (Medical University of Bialystok) and Associate Prof. Mirosław Kwasniewski, PhD (Medical University of Bialystok, IMAGENE.ME), advanced associative analyses were carried out to identify clinical features and genetic variants in the Polish population associated with severe COVID-19. The research was conducted in cooperation with the Institute of Tuberculosis and Lung Diseases in Warsaw and 15 clinical units from all over Poland. Highly precise genome profiling using exome sequencing technology (WES) was performed on more than 1,400 patients infected with SARS-CoV-2 with different clinical stages of COVID-19 disease. Based on several phenotypic, clinical and genetic parameters, a model was developed to estimate the chances of severe COVID-19. The mathematical model has been adapted in the form of a risk calculator, which can be used by clinical institutions throughout Poland.