Genetic variants linked to long-term illness risk following viral infection

Twenty-two genes associated with the risk of developing chronic conditions following a viral infection have been identified.

The Epstein-Barr virus (EBV) is a common virus that infects 90 percent of the population during their lifetimes, commonly causing glandular fever which lasts a few weeks. Researchers in the UK and USA collaborated to understand why, in some people, it appears to contribute to triggering chronic diseases, such as lupus, heart disease and some cancers.

'This research adds a missing piece to the puzzle of chronic disease. We show that genetic variation influences how well EBV is controlled, and that poorer viral control is associated with several long-term illnesses,' said Dr Ryan Dhindsa, assistant professor of pathology and immunology at Baylor College of Medicine, Houston, Texas and co-corresponding author of the study published in Nature.

Using data from the UK Biobank and the US All of Us cohort, the researchers analysed whole-genome sequencing data from over 700,000 participants. It was found that 9.7 percent of participants had higher levels of EBV DNA in their cells after infection, compared to others.

They found 22 regions of the genome associated with these higher levels of EBV, leading the authors to suggest that some people may be more vulnerable to EBV due to a genetic predisposition.

'Identifying the roles of these 22 genes that are a significant factor in EBV control offers a profound leap forward,' said co-corresponding author Dr Slavé Petrovski, from the AstraZeneca Centre for Genomics Research in Cambridge.

'We found that people with higher EBV levels are about 50 percent more likely to have rheumatoid arthritis and nearly twice as likely to have COPD compared to those with lower levels. Insight into the genetic drivers behind this not only helps us understand who is at greater risk of longer-term disease burden but also informs the next wave of research into therapeutic and potentially early intervention strategies,' he added.

Many of the genetic differences found were within immune system genes, specifically those encoding the major histocompatibility complex. These proteins are responsible for finding harmful pathogens within the body. The variants may make it more difficult for the body to detect and control the EBV virus.

The specific variants that were associated with poor EBV control were also linked to other autoimmune conditions like rheumatoid arthritis and lupus, strengthening the theory that the virus may be involved in causing certain autoimmune conditions.

'These findings suggest that health outcomes reflect a complex interaction between our genes, lifestyle, and viral history. While further work is needed to determine which of these links are causal, the results point to new ways to identify risk and guide future efforts to prevent and treat chronic disease,' said Dr Dhindsa.