New data analysis from the Veterans Affairs Million Veteran Program (MVP) has uncovered genetic links between COVID-19 severity and certain medical conditions it can cause, including venous embolism and thrombosis, type 2 diabetes, ischemic heart disease, and neutropenia. Identifying these shared variants could improve understanding of COVID-19 and point to new paths for treatment.
The study was led by Anurag Verma of the Corporal Michael Crescenz VA Medical Center in Philadelphia. The team’s findings were presented this week in PLOS Genetics.
Verma said, “The study demonstrates the value and impact of large biobanks linking genetic variations with EHR data in public health response to the current and future pandemics. MVP is one of the most diverse cohorts in the US. We had a unique opportunity to scan thousands of conditions documented before the COVID-19 pandemic. We gained insights into the genetic architecture of COVID-19 risk factors and disease complication.”
About one in six COVID-19 patients will have serious symptoms. Certain genetic links associated with a person’s risk of more severe COVID-19 have already been uncovered. For example, certain APOL1 variants raise the risk of kidney injury and death in Black patients. In women, meanwhile, telomere length seems to have impact on disease severity. The virus also causes severe inflammation in just a subject of patients.
According to this team’s work, specific variants may be associated with other medical conditions that are already be well understood.
To identify shared variants, Verma and colleagues used the MVP’s large set of genotypic information linked to electronic health record data (EHR) for more than 650,000 U.S. veterans. The team conducted phenome-wide association study (PheWAS) to examine links between variants often found in Veterans who experienced severe COVID-19 and variants associated with a broad selection of medical conditions.
The analysis revealed that certain variants associated with COVID-19 are also associated with other conditions that sometimes occur with the infection. Links were found for variants associated with venous embolism and thrombosis, as well as type 2 diabetes and ischemic heart disease—two known COVID-19 risk factors.
The analysis also found genetic links between severe COVID-19 and neutropenia for Veterans of African and Hispanic ancestry; these links did not appear for those of European ancestry.
Among respiratory conditions, idiopathic pulmonary fibrosis and chronic alveolar lung disease shared genetic links with severe COVID-19, but other respiratory infections and chronic obstructive pulmonary disease (COPD) did not. Some variants associated with severe COVID-19 were also associated with reduced risk of autoimmune conditions, such as psoriasis and lupus. These findings highlight the need to carefully weigh various aspects of the immune system when developing new treatments.
Despite some limitations of the PheWAS method, these findings could help deepen understanding of COVID-19 and guide development of new treatments.
“One thing that stood out to us was the high number of immune-mediated conditions that shared genetic architecture with severe manifestations of COVID-19,” coauthor Katherine Liao adds. “The nature of the associations brought to light how the SARS-CoV2 virus pushes on a pressure point in the human immune system and its constant balancing act of fighting infection while maintaining enough control so that it does not also become an autoimmune process, attacking self.”
