Association between schizophrenia risk allele dosage of rs6994992 and whole-brain structural and functional characteristics

Abstract

The rs6994992 polymorphism has been reported as a candidate variant associated with schizophrenia (SZ). Neuroimaging studies have revealed that SZ is associated with widespread structural and functional alterations in brain. However, whether the allele dosage of rs6994992 is associated with brain structural or functional features is unclear. We aimed to investigate the association between the risk allele dosage of rs6994992 and whole-brain structural and functional characteristics and to further explore the relationship between these characteristics and cognition. Magnetic resonance images and the rs6994992 genotype were obtained from 53 healthy participants. A general linear model was used to determine the effects of risk allele dosage of rs6994992 on brain characteristics. Spearman correlation analysis was employed to calculate the correlation between altered brain characteristics and cognitive scores. Our results demonstrated that regions with significant differences in structural characteristics between groups with different dosages of rs6994992 were mainly located in the frontal and temporal lobes, hippocampus and angular gyrus. Moreover, significant regions of functional connectivity (FC) partly overlapped with the structural results. Measurements in those significant regions and FCs were correlated with the cognition scales. This association can inform our understanding of the mechanisms through which rs6994992 variants increase the risk for SZ.