Potential genetic risk factors for COVID-19 identified

A study that combined genetic information with an examination of lung gene expression identified genetic risk variants in the ABO gene that might significantly increase the chances of incurring COVID-19.

Susceptibility and severity of COVID-19 are determined by a complex interaction of genetics and environmental exposures. The genes that influence the pathophysiology of COVID-19 have yet to be identified. 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 and identify candidate genes for this disease. “Genetic associations alone cannot pinpoint the exact gene responsible for COVID-19,” said Dr Hernandez Cordero. “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.”

Genetic information was combined with an examination of lung and blood gene expression to identify significant associations with COVID-19. Specific gene markers were identified that share their effects on gene expression and protein levels with COVID-19 susceptibility. For the analysis, the following bioinformatics parameters 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, several genes were found to be responsible for the immune response to COVID-19 and were also involved in COVID-19 susceptibility. These results were in line with findings of previous research.

Looking for candidate genes in blood proteins, they were able to go one step further in connecting the effect of genes on susceptibility to COVID-19. Blood proteomics can also help identify blood markers that might be used to indicate disease status and, potentially, to monitor the disease. “By harnessing the power of genomic information, we identified genes related to COVID-19,” said Dr Hernandez Cordero. Increased levels of ABO in plasma were causally associated with an increased risk of COVID-19, whereas the blood group O showed to be protective against COVID-19.

In addition to the ABO gene, Dr Hernandez Cordero and colleagues found that 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. Furthermore, these genes may prove to be good markers for disease as well as potential drug targets,” she concluded.

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

Posted on 18 May, 20214 August, 2021