ROBO1 polymorphisms, callosal connectivity, and reading skills.

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.