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A new analysis of gene expression and protein content in lung and blood tissue subscription Genes that play a central role in determining blood type can also affect susceptibility to COVID-19. Researchers at the University of British Columbia analyzed data from three studies to correlate gene and protein expression in lung and blood with gene regions associated with COVID-19 susceptibility.
“These genes are excellent markers of disease and potential drug discovery targets,” said Dr. Anahernandez Cordero, a postdoctoral fellow at the Center for Cardiopulmonary Innovation at the University of British Columbia (Vancouver, Canada). That could be proven. ” statement. Cordero presented his work at the American Thoracic Society (ATS) 2021 International Conference held online.
Cordero said genome-wide association studies have been used to identify gene regions associated with COVID-19 susceptibility, but cannot be used to identify specific genes. To identify the genes, the researchers adopted integrated genomics that combined Mendelian randomization and Mendelian randomization based on Bayesian co-localization summaries.
Search for candidate genes
Researchers have combined genetic and transcriptomics data, which are measurements of intracellularly generated messenger RNA. Messenger RNA is used as a blueprint for protein production.Genetic data came from COVID-19 Host Genetics Initiative Genome-wide related meta-analysis version 4 (patients with COVID-19 and patients without COVID-19). Blood transcriptomics data interval Study (n = 3301), and lung transcriptomics data Lung eQTL Study (n = 1038). “From the integration of these three datasets, we identified the candidate genes most likely to affect COVID-19 through gene expression. We also investigated the most consistent candidate genes for plasma protein levels and COVID. -19 We tested a causal relationship with susceptibility. Basian co-localization and Mendel randomization. “
Researchers have identified six genes expressed in the lung and five genes expressed in the blood that co-localize with the COVID-19 susceptibility locus.They found that increased plasma levels of ABO were associated with a greater risk of COVID-19 (Mendelia Randomization). P = .000025) And its expression SLC6A20 gene The risk of COVID-19 in the lungs was also increased. They also discovered new associations in genes associated with respiratory disease, including: asthma, And genes associated with the host’s immune response, such as the number of neutrophils and eosinophils.
Within subscription Genes, studies have also revealed evidence that blood group O may be protective against COVID-19. “The most important mutant used in the Mendelian randomized trials was a complete linkage mismatch with the mutant responsible for blood group O genotype, resulting in a reduced risk,” said Cordero. I am.
The method of this study is a powerful method, said Dr. Jeremy Alexander Hirota, who was asked to comment. “This study uses integrated omics to determine COVID-19 susceptibility factors that were difficult to identify with a single technique,” said McMaster University Associate Professor and University Biology Associate Professor. Mr. Hirota said. Associate Professor of Medicine at Waterloo and the University of British Columbia. He trained with senior authors of the study, but was not directly involved in the study.
It is not surprising that the host’s genes can be identified, according to Hirota, as it is widely believed that the host’s response is responsible for the symptoms of COVID-19. However, the identification of variants of the ABO protein is interesting. It suggests that systemic effects beyond respiratory mucosal immunity are the driving force of susceptibility. In my understanding, the ABO protein is not expressed in the respiratory mucosa, which is a common site of initial contact with SARS-CoV-2. The association between blood ABO levels and early infection of the respiratory mucosa with SARS-CoV-2 is unclear. “
Severity link required
Hirota also noted that the study was associated with susceptibility to COVID-19, but it is not clear from the available data whether such association is associated with disease severity. It was. “if [patients with gene variants] More susceptible [the disease is] If not so serious, the results should be interpreted accordingly. Work conveys a much more important message when susceptibility and severity increase, which can be measured by ICU admission, ventilator use, or increased risk of death. To better understand the clinical usefulness of these findings for optimal management of COVID-19 patients, future studies are needed to extend this study and integrate severity measurements. ” He said.
It is also unclear whether the population studied reflects the population currently at highest risk of COVID-19, such as residents of India, who are currently at increased risk of disease.
Cordero and Hirota do not disclose the relevant financial relationship.
American Thoracic Society (ATS) 2021 International Conference: Summary A3765.. Announced on May 14, 2021.