MIR137polygenic risk is associated with schizophrenia and affects functional connectivity of the dorsolateral prefrontal cortex

Background Genome-wide association studies (GWAS) have consistently revealed that a variant of microRNA 137 (MIR137) shows a quite significant association with schizophrenia. Identifying the network of genes regulated byMIR137could provide insights into the biological processes underlying schizophrenia. In addition, DLPFC functional connectivity, a robust correlate ofMIR137,may provide plausible endophenotypes. However, the regulatory role of theMIR137gene network in the disrupted functional connectivity remains unclear. Here, we tested the effects of theMIR137regulated genes on the risk for schizophrenia and DLPFC functional connectivity. Methods To evaluate the additive effects of theMIR137regulated genes (N= 1274), we calculated aMIR137polygenic risk score (PRS) for schizophrenia and tested its association with the risk for schizophrenia in the genomic data of a Han Chinese population that included schizophrenia patients (N= 589) and normal controls (N= 575). We then investigated the association betweenMIR137PRS and DLPFC functional connectivity in two independent young healthy cohorts (N= 356 andN= 314). Results We found that theMIR137PRS successfully captured the differences in genetic structure between the patients and controls, but the single geneMIR137did not. We then consistently found that a higherMIR137PRS was correlated with lower functional connectivities between the DLPFC and both the superior parietal cortex and the inferior temporal cortex in two independent cohorts. Conclusion The findings suggested that these two functional connectivities of the DLPFC could be important endophenotypes linking theMIR137-regulated genetic structure to schizophrenia.