Host genetics and daily rhythms shape the human DNA virome
A massive multi-cohort study analyzed DNA viral load for 31 viruses in blood and saliva, finding that viral load varies with age, sex, time of day, and season, and is higher in men. Genome-wide associations implicate dozens of loci, especially in the MHC/HLA region, and genes like ERAP1/ERAP2 in shaping EBV, HHV-7, HHV-6B and other viral loads, with notable virus-specific effects and EBV subtype interactions. Saliva shows frequent lytic bursts for some herpesviruses, contrasting with blood. Mendelian randomization suggests higher EBV DNA load may causally increase Hodgkin’s lymphoma risk but not multiple sclerosis, highlighting a host-genome influence on the circulating DNA virome and its disease connections; the findings also reveal ancestry- and tissue-specific patterns and circadian/seasonal dynamics.