Researchers Identify Genes Associated With Significant Increase in COVID-19 Risk

Having genetic risk variants in the ABO gene could significantly increase the chances of developing COVID-19, and other genes could also increase COVID-19 risk, according to research presented at the ATS 2021 International Conference.

Much about COVID-19 remains a medical mystery, including whether certain genes put individuals at greater risk of contracting the SARS-CoV-2 virus, which causes COVID-19. Ana Hernandez Cordero, PhD, postdoctoral fellow at the Center for Heart Lung Innovation, University of British Columbia, and colleagues used integrative genomics in conjunction with proteomics to identify these genes.

Genomics research identifies specific genes that can play a role in biological processes such as the development of diseases, while proteomics does the same for proteins. Researchers can gain a more complete picture of disease processes by integrating tools to investigate both.

“DNA is a large, complex molecule and so genetic associations alone cannot determine the exact gene responsible for COVID-19,” said Dr. Hernandez. “However, by combining genetic information from COVID-19 with gene expression and proteomic datasets, we can find out which genes drive the relationship with COVID-19.”

The researchers combined genetic information with a lung gene expression study to identify genetic variants that controlled gene expression in the lung and were responsible for COVID-19. The researchers identified specific markers of genes that share their effects on gene expression and protein levels with COVID-19 sensitivity. For the analysis, they used bioinformatics to integrate: (1) a genomic dataset obtained from both patients infected with SARS-CoV-2 and uninfected individuals (controls); (2) lung and blood tissue gene expression datasets from clinical populations (non-COVID-19); and (3) a proteome data set obtained from blood donors (non-COVID-19).

By doing this, they found that several genes responsible for the immune system’s response to COVID-19 are also involved in COVID-19 sensitivity. What they discovered was supported by the findings of previous research.

Searching for candidate genes in blood proteins allowed them to go a step further in linking the effects of genes to COVID-19 sensitivity. Blood proteomics can also help identify markers in the blood that can be easily measured to indicate disease status and possibly monitor disease.

“Using the power of genomic information, we have identified genes related to COVID-19,” said Dr. Hernandez. “In particular, we discovered that the ABO gene is an important risk factor for COVID-19. Of particular interest was the relationship between ABO blood group and COVID-19 risk. We have shown that the relationship is not only a relationship, but also a causal relationship. “

In addition to the ABO gene, Dr. Hernandez and colleagues found that people with certain genetic variants for SLC6A20, ERMP1, FCER1G and CA11 have a significantly higher risk of contracting COVID-19. “These people have to be extremely careful during the pandemic. These genes may also prove to be good markers of disease and potential drug targets. “

Several of the genes identified in the researchers’ analysis have already been linked to respiratory diseases. For example, ERMP1 has been linked to asthma. CA11 can also increase COVID-19 risk for people with diabetes.

Genetic associations for COVID-19 and gene and protein expression were combined using integrative genomics (IG). IG wants to identify mechanisms (for example, gene expression levels) that link the effects of the genetic code to a complex disease. These methods, while complex, are also fast and their results can help researchers prioritize candidate genes for in vitro (in the laboratory) and in vivo (in living organisms) testing.

Dr. Hernandez added, “Our research has progressed since 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 the increasing evidence suggests that these candidates and their role in COVID-19 need to be further explored. “

Reference: “Integrative Genomic Analysis Highlights Potential Genetic Risk Factors for Covid-19” by AI Hernandez Cordero, X. Li1, S. Milne, C. Yang, Y. Bossé, P. Joubert, W. Timens, M. Van den Berge, D. Nickle, K. Hao and DD Sin, May 3, 2021, ATS 2021 International Conference.
Abstract