Genes associated with gray matter volume alterations in schizophrenia

Although both schizophrenia and gray matter volume (GMV) show high heritability, however, genes accounting for GMV alterations in schizophrenia remain largely unknown. Based on risk genes identified in schizophrenia by the genome-wide association study of the Schizophrenia Working Group of the Psychiatric Genomics Consortium, we used transcription-neuroimaging association analysis to test that which of these genes are associated with GMV changes in schizophrenia. For each brain tissue sample, the expression profiles of 196 schizophrenia risk genes were extracted from six donated normal brains of the Allen Human Brain Atlas, and GMV differences between patients with schizophrenia and healthy controls were calculated based on five independent case-control structural MRI datasets (276 patients and 284 controls). Genes associated with GMV changes in schizophrenia were identified by performing cross-sample spatial correlations between expression levels of each gene and case-control GMV difference derived from the five MRI datasets integrated by harmonization and meta-analysis. We found that expression levels of 98 genes consistently showed significant cross-sample spatial correlations with GMV changes in schizophrenia. These genes were functionally enriched for chemical synaptic transmission, central nervous system development, and cell projection. Overall, this study provides a set of genes possibly associated with GMV changes in schizophrenia, which could be used as candidate genes to explore biological mechanisms underlying the structural impairments in schizophrenia.