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Not every child seems equally susceptible to the same parental, educational, or environmental influences even if cognitive level is similar. This study is the first randomized controlled trial to apply the differential susceptibility paradigm to education in relation to children's genotype and early literacy skills. A randomized pretest–posttest control group design was used to examine the effects of the Intelligent Tutoring System Living Letters. Two intervention groups were created, 1 receiving feedback and 1 completing the program without feedback, and 1 control group. Carriers of the long variant of the dopamine D4 receptor gene (DRD4 7-repeat) profited most from the computer program with positive feedback, whereas they performed at the lowest level of early literacy skills in the absence of such feedback. Our findings suggest that behind modest overall educational intervention effects a strong effect on a subgroup of susceptible children may be hidden.