We detected sub-additive interaction of stx1a and stx2a. After accounting for age and symptoms, when stx1a and stx2a occur together in E. coli O157:H7 (i.e., as the stx1a2a genotype), the risk of HUS was 27.1% lower (95% CI −87.8%, −2.3%) than would be expected if interaction were not present, based on the risk of HUS associated with the stx1a-only and stx2a-only genotypes (Figure S2, Supplemental Results). Here, STX2 is linked to hemolytic-uremic syndrome.