22 Genes Linked to Chronic Epstein-Barr & Risks of MS, Cancer

Around 90% of people are infected with the Epstein-Barr virus (EBV) at some point in their lives. For most, this results in a mild, short-lived illness commonly known as mononucleosis, or mono. However, for a subset of individuals, EBV can contribute to the development of chronic illnesses, including certain cancers and autoimmune disorders.

New research is shedding light on the genetic factors that may predispose individuals to these chronic conditions following an EBV infection. A study published in Nature on January 18, 2026, identified 22 human genes potentially linked to a higher risk of developing chronic illness after EBV infection.

Researchers emphasize that it remains unclear whether these genes directly increase the danger posed by EBV, or if they are associated with underlying immune system weaknesses that allow the virus to persist at higher levels within the body. However, the findings provide a crucial starting point for further investigation, according to experts.

“My lab is already looking into the results and thinking about what we can learn from this and what other avenues of research it suggests,” said Jill Hollenbach, a professor of neurology at the University of California, San Francisco, who was not involved in the study.

Understanding Epstein-Barr Virus and Its Long-Term Effects

Epstein-Barr virus is known for causing mononucleosis, characterized by significant fatigue. However, even after the acute symptoms of mono subside, the virus remains dormant within the body, primarily residing in B cells – a type of immune cell responsible for remembering and defending against specific pathogens.

While this latent EBV presence typically causes no harm, in some individuals, the virus remains active at a higher level. This persistent activity has been linked to an increased risk of certain nasopharyngeal cancers and lymphomas, as well as potentially contributing to autoimmune disorders like multiple sclerosis. Emerging research also suggests a connection between chronic, active EBV and heart and lung disease.

A Novel Approach to Identifying Genetic Links

To understand why only certain individuals develop chronic illnesses following EBV infection, researchers at Baylor College of Medicine took a unique approach. Led by Ryan Dhindsa, the team analyzed data from large-scale human DNA biobanks – repositories that collect genetic information and health records from hundreds of thousands of people.

Traditionally, when analyzing human genome sequence data, researchers discard genetic reads that don’t match the human reference genome. Dhindsa and his team decided to examine these discarded reads, hypothesizing they might contain viral DNA. “Typically, when we’re analyzing human genome sequence data we ignore the reads that don’t map back to a human reference genome. We just kind of throw them away,” Dhindsa explained. “Here, we decided maybe we could go through those reads that we normally throw away and see if we could recover viral DNA.”

By analyzing data from the UK Biobank and the U.S. National Institutes of Health’s All of Us biobank, encompassing approximately 750,000 individuals, the researchers identified around 11% of participants with high levels of EBV DNA. These individuals were more likely to have health conditions previously associated with EBV, including diseases of the spleen and Hodgkin lymphoma.

Associations were also observed with conditions suspected to be linked to EBV, though with less certainty: rheumatoid arthritis, chronic obstructive pulmonary disease (COPD) and lupus. Further analysis revealed connections between EBV and conditions like heart disease, kidney failure, stroke, and depressive episodes.

The Role of 22 Key Genes

In addition to identifying individuals with high viral loads, the study pinpointed 22 genes associated with a greater likelihood of persistent EBV infection. Many of these genes are located within the human leukocyte antigen (HLA) locus, a region of the genome responsible for coding immune cells that present antigens to the immune system.

“It seems like these variants changed the way an individual’s immune response actually presents Epstein-Barr virus to the immune system,” Dhindsa said, potentially hindering the body’s ability to control viral replication. However, he cautioned that further research is needed to establish a definitive cause-and-effect relationship.

The researchers also identified variations in genes that regulate the immune system, including SLAMF7, which encodes a protein involved in natural killer cell-mediated tumor cell destruction, and CTLA4, which encodes a receptor on T cells that helps prevent autoimmune responses.

Future Directions and Implications

Hollenbach emphasized the significance of these findings, stating, “They found some really interesting results.” Her team is now focused on investigating the mechanisms linking genetic variations to the immune response to EBV.

Dhindsa and his colleagues plan to expand their research to include other viruses with long-term health impacts, such as Merkel cell polyomavirus and human T-cell lymphotropic virus type 1. They also aim to incorporate data from more diverse global populations, acknowledging that the current datasets—particularly the UK Biobank—are predominantly of European ancestry.

“We need to be able to look at genetic differences across more representative samples in future work,” Dhindsa stated.