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Noroviruses are a leading cause of acute gastroenteritis. Genogroup 2 type 4 (GII.4) has been the dominant norovirus genotype worldwide since its emergence in the mid-1990s. Individuals with a functional fucosyltransferase-2 gene, known as secretors, have increased susceptibility to GII.4 noroviruses. We hypothesized that this individual-level trait may drive GII.4 norovirus predominance at the human population level.