LAUSR

The genetic effects on specific behavioral phenotypes are putatively mediated by specific neural functions. It remains unexplored how the axon‐guidance‐receptor gene ROBO1 influences reading performance through the neural system despite the identification of ROBO1 as a susceptibility gene for dyslexia. To address this issue, the present study recruited a group of children with a wide range of reading abilities. Two previously identified reading‐related ROBO1 polymorphisms were genotyped, and diffusion and structural MRI were acquired to measure the fiber microstructure of the corpus callosum (CC), the major white‐matter tract that connects inter‐hemispheric cortical regions. The results confirmed the significant influence of the ROBO1 polymorphisms on reading scores. The fiber microstructures of the midline‐CC segments around the genu and splenium were also affected by the ROBO1 polymorphisms. Moreover, a mediation analysis further revealed that the genu could significantly mediate the effects of the ROBO1 polymorphisms on word‐list reading performance, which suggests a ROBO1‐to‐genu‐to‐reading pathway. The genu‐linked cortical morphology, however, was not associated with either the ROBO1 polymorphisms or reading performance. These findings offer direct evidence supporting ROBO1‐callosum association in humans and also provide valuable insight into the functions of ROBO1 and the gene‐to‐brain mechanisms that underlie human reading. Hum Brain Mapp 38:2616–2626, 2017. © 2017 Wiley Periodicals, Inc.