Much about COVID-19 remains a medical mystery. Which genes cause COVID-19 and which genes place someone at a greater risk remains unclear.
To find out the answer to these questions, a new study used integrative genomics combined with proteomics.
Ana Hernandez Cordero, Ph.D., a postdoctoral fellow with the Centre for Heart Lung Innovation, University of British Columbia, said, “DNA is a big, complex molecule and so, genetic associations alone cannot pinpoint the exact gene responsible for COVID-19. 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.”
Scientists combined genetic information with an examination of lung gene expression. They identified genetic variants that were controlling gene expression in the lung that was responsible for COVID-19.
Specific genes’ markers were identified to sharing their effects on gene expression and protein levels with COVID-19 susceptibility.
Scientists also used bioinformatics for the analysis to integrate: (1) a genomic dataset obtained from patients who were infected with SARS-CoV-2 as well as non-infected individuals (controls); (2) lung and blood tissue gene expression datasets from clinical populations (non-COVID-19); and (3) a proteome dataset obtained from blood donors (non-COVID-19).
Doing so, scientists were able to find several genes that play a vital role in the immune system’s response to COVID-19. These genes are also found t be involved in COVID-19 susceptibility.
Dr. Hernandez said, “By harnessing the power of genomic information, we identified genes that are related to COVID-19. In particular, we found that the ABO gene is a significant risk factor for COVID-19. Of particular note was the relationship between the blood group ABO and COVID-19 risk. We showed that the relationship is not just an association but causal.”
Along with the ABO gene, it was found that people carrying specific genetic variants for SLC6A20, ERMP1, FCER1G, and CA11 have a significantly higher risk of contracting COVID-19.
Dr. Hernandez said, “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.”
Some of these genes were found to be linked with respiratory diseases. For example, ERMP1 has been linked to asthma. CA11 may also elevate COVID-19 risk for people with diabetes.
Dr. Hernandez added, “Our research has progressed since the time that we first conducted this analysis. We have now identified even more interesting candidates for COVID-19, such as IL10RB, IFNAR2, and OAS1. These genes have been linked to severe COVID-19. Their role in the immune response to viral infections and mounting evidence suggests that these candidates and their role in COVID-19 should be further investigated.”