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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 ran- domized 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 feed- back, 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.