Polymorphism in schizophrenia risk gene MIR137 is associated with the posterior cingulate Cortex's activation and functional and structural connectivity in healthy controls

Abstract

MIR137 gene has been repeatedly reported as a schizophrenia risk gene in genome-wide association studies (GWAS). A polymorphism (rs1625579) at the MIR137 gene has been associated with both neural activation and behavioral performance during a working memory task. This study examined MIR137's associations with task-related (N-back working memory) fMRI, resting state fMRI, and diffusion tensor images (DTI) data in 177 healthy adults. We found less deactivation of the PCC in risk allele homozygotes (TT) as compared to the GT heterozygotes (cluster size = 630 voxels, cluster level PFWE < 0.001) during the N-back task, which replicated previous findings. Using the identified cluster within the PCC as the seed, we further found decreased functional connectivity between the PCC and the anterior cingulate cortex and its adjacent medial prefrontal cortex (ACC/MPFC) in risk allele homozygotes during both resting state (cluster size = 427 voxels, cluster level PFWE = 0.001) and the N-back task (cluster size = 73 voxels, cluster level PFWE = 0.05). Finally, an analysis of our DTI data showed decreased white matter integrity of the posterior cingulum in risk allele homozygotes (cluster size = 214 voxels, cluster level PFWE = 0.03). Taken together, rs1625579 seems to play an important role in both functional and structural connectivity between the PCC and the ACC/MPFC, which may serve as the brain mechanisms for the link between rs1625579 and schizophrenia. Keywords: MIR137 gene, Working memory, Functional connectivity, Structural connectivity, Posterior cingulate cortex