Abstract: Background: Although intelligence is thought to be heritable, there is evidence for environmental effects on cognitive performance as evidenced by a strong increase in average intelligence in the second half of the previous century (FlynnEffect). It is highly suggestive that environmental factors interact with genotype by regulation of gene expression and thus contribute to individual malleability. This might be re- flected in recent observations of an association between the dopamine-dependent encoding of reward prediction errors and intelligence, which was modulated by environmental factors. Methods: In a sample of 1475 young healthy adolescents from the IMAGEN cohort, general IQ was assessed. As predictors, we used polygenic scores for intelligence, methylation count in CpG-islands relevant for dopaminergic neurotransmission, gray matter in the striatum and brain activation elicited by temporarily surprising reward-predicting cues. Results: We could show, that IQ is positively associated with 1) polygenic scores for intelligence (3.2% of variance explained, p¼7.3x10-8), 2) epigenetic modification of DRD2 gene (2.7%, p¼3.2x10-4), 3) gray matter density in the striatum (0.71%, p¼1.7x10-3), and 4) functional activation during reward anticipation (1.4%, p¼4.1x10-6). Comparing the relative importance in an overlapping subsample, our results point to the equal importance of genetic variance, epigenetic modification, as well as functional activation. Conclusions: Our findings suggest that functional activation of the reward system, epigenetic control of dopaminergic neurotransmission and genetic markers contribute equally to IQ. Peripheral epigenetic markers are in need of confirmation in the central nervous system and should be tested specifically assessing individual and social stress factors that can modify the epigenetic markers.