Less Efficient Information Transfer in Cys-Allele Carriers of DISC1: A Brain Network Study Based on Diffusion MRI

Abstract

Previous neuroimaging studies of brain networks have revealed less efficient information transfer in patients with schizophrenia. However, the underlying genetic basis remains largely unexplored. In this study, we investigated the brain anatomical networks of 278 healthy volunteers with different genotypes in the common missense variant (Ser704Cys) of the Disrupted-in-Schizophrenia-1 (DISC1) gene, which is one of the main susceptibility genes of schizophrenia and other psychiatric disorders. The anatomical brain network for each individual was constructed using fiber tractography technique based on diffusion magnetic resonance imaging (dMRI). The properties of this network were then calculated using graph theory. This revealed that Cys-allele carriers showed significantly lower global efficiency of their brain networks than Ser homozygotes, thereby supporting our hypothesis that genetic variation in DISC1 may relate to the risk of schizophrenia by affecting the efficiency of brain network. Additional dMRI analyses were also performed at different levels, with a convergent trend towards decreased white matter integrity being consistently observed in Cys-allele carriers. Together these findings not only provide new clues for understanding DISC1 function, but also suggest that network analyses based on graph theory combined with neuroimaging techniques may reveal structural disruptions related to genetic risk in the brains of healthy individuals.