Early-life rotavirus infection susceptibility and later gastrointestinal cancer protection: Reverse antagonistic pleiotropy and potential vaccine benefits
Highlights • Whole-exome sequencing in severe rotavirus cases identified seven candidate SNPs, several linked to gastrointestinal cancer pathways. • Transcriptomic and epigenomic data supported functional involvement of top candidate genes and suggested roles in cancer progression. • Polygenic risk score analyses indicated reduced gastrointestinal cancer risk among individuals with severe early-life RV infection. • Evidence of recent positive selection in key SNPs supports a model of reverse antagonistic pleiotropy, suggesting early RV susceptibility may confer later-life cancer protection.