Genetic risk variants responsible for COVID-19 predisposition

The susceptibility and severity of a SARS-CoV-2 infection are determined by a complex interaction of genetics and environmental exposures. A study that combined genetic information with gene expression and proteomic datasets identified genetic risk variants in the ABO gene that might significantly increase the chances of a SARS-CoV-2 infection.

The aim of the study presented by Dr Ana Hernandez Cordero (Centre for Heart Lung Innovation, University of British Columbia, Canada) was to use integrative genomics to combine gene expression and proteomic information with COVID-19 susceptibility [1]. Genomic research identifies specific genes that may play a role in biological processes such as the development of disease, while proteomics does the same for proteins. The combination of both approaches allows researchers to get a fuller picture of disease processes. “Genetic associations alone cannot pinpoint the exact gene responsible for COVID-19,” said Dr Hernandez. “However, by combining COVID-19 genetic information with gene expression and proteomic datasets, we can figure out which genes are driving the relationship with COVID-19.”

The COVID-19 Host Genetics Initiative has been founded to identify genetic determinants of COVID-19 susceptibility and severity and share the results from such activities [2]. The researchers combined genetic information with an examination of lung gene expression to identify genetic variants which control gene expression in the lung that were responsible for COVID-19. They identified specific gene markers that share their effects on gene expression and protein levels with COVID-19 susceptibility. For the analysis, the following bioinformatics were integrated:

• a genomic dataset obtained from patients who were infected with SARS-CoV-2 as well as non-infected individuals (controls);
• lung and blood tissue gene expression datasets from clinical populations (non- COVID-19); and
• a proteome dataset obtained from blood donors (non-COVID-19).

With this method, it was found that several genes responsible for the immune system’s response to COVID-19 are also involved in COVID-19 susceptibility. These findings were in line with previous research.

By exploring candidate genes in blood proteins, the effects of genes could be connected to susceptibility to COVID-19. Blood proteomics can also identify markers in the blood that can be easily measured to indicate disease status and, potentially, monitor the disease. “By harnessing the power of genomic information, we identified genes that are related to COVID-19,” said Dr Hernandez. Increased levels of ABO in plasma were associated with an increased risk of COVID-19, whereas the blood group O appeared protective against COVID-19.

In addition to the ABO gene, people carrying certain genetic variants for SLC6A20, ERMP1, FCER1G, and CA11 had a significantly higher risk of contracting COVID-19. “These individuals should use extreme caution during the pandemic. These genes may also prove to be good markers for disease as well as potential drug targets,” Dr Hernandez concluded.

Several of the genes identified in this analysis have already been linked with respiratory diseases. For example, ERMP1 has been associated with asthma and CA11 may also elevate COVID-19 risk for people with diabetes.

1. AI Hernandez Cordero. Integrative genomic analysis highlights potential genetic risk factors for Covid-19. TP91: Lung infection (Non-mycobacterial, i.e., bacterial, viral, fungal, HIV, etc). ATS 2021 International conference, 14-19 May 2021.

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Posted on 5 July 2021