EBV DNA positivity links to MS risk genes in a cross-ancestry study of 617,186 participants.

This cross-ancestry genome-wide association study evaluated data from 617,186 individuals to explore the genetic overlap between Epstein-Barr virus (EBV) infection and multiple sclerosis (MS). The primary exposure was EBV DNA positivity, assessed against genetic susceptibility profiles. The study aimed to clarify whether specific EBV infection states correlate with MS risk loci.

The analysis identified 39 susceptibility risk loci that overlapped with established MS risk genes, with a statistical significance of p=1.3x10-12. Additionally, researchers detected 1,069 EBV-infected B cells across 38 individuals within the cohort. The viral infection was predominantly observed in the latent phase, and B cell differentiation appeared altered by the infection.

Further examination revealed that EBV-infected switched memory and atypical B cells exhibited upregulated cytokines and costimulatory signals. Furthermore, EBV-infected memory B cells showed upregulation of risk genes from both the EBV and MS pathways. These molecular changes provide insight into potential mechanisms linking viral infection to autoimmune susceptibility.

The study did not report specific safety data, adverse events, or tolerability metrics. Key limitations include the observational nature of the cross-ancestry design, which precludes definitive causal conclusions. While the genetic overlap is statistically robust, the findings describe associations rather than establishing direct causation between EBV infection and MS development.