EP 228: What genomes reveal about EBV and human disease with Ryan Dhindsa and Caleb Lareau

In this episode of The Genetics Podcast, host Patrick Short interviews Dr. Ryan Dhindsa and Dr. Caleb Lareau about their collaborative research on Epstein-Barr virus (EBV) persistence and its links to human disease. The conversation begins with the origin of their collaboration, sparked by a Twitter DM, and details their method of extracting EBV sequences from existing human whole-genome sequencing data, particularly from the UK Biobank. They validated their computational approach using serology data from a subset of participants, overcoming initial challenges with repetitive elements. Their genome-wide association study identified 22 loci associated with EBV persistence, with the strongest signal in the MHC region. They found genetic correlations with autoimmune diseases like lupus and rheumatoid arthritis, but notably not with multiple sclerosis, suggesting a ‘hit and run’ mechanism for MS versus a chronic antigen stimulation model for other conditions. The discussion also covers the broader implications for computational virology, the potential to extend this approach to other DNA viruses, and design considerations for future population genomics programs, including the need for longitudinal samples and raw data availability. The episode concludes with insights into each researcher’s broader research interests, including rare variant genetics and the human virome.