Identification of genetic features that are associated with amplitude of low-frequency fluctuation changes in schizophrenia using omics analysis

Abstract

Genetic risk for schizophrenia is thought to trigger variation in clinical features of schizophrenia, but biological processes associated with neuronal activity in brain regions remain elusive. In this study, gene expression features were mapped to various sub-regions of the brain by integrating low-frequency amplitude features and gene expression data from the schizophrenia brain and using gene co-expression network analysis of the Allen Transcriptome Atlas of the human brain from six donors to identify genetic features of brain regions and important associations with neuronal features. The results indicate that changes in the dynamic amplitude of low-frequency fluctuation (dALFF) are mainly associated with transcriptome signature factors such as cortical layer synthesis, immune response, and expanded membrane transport. Further modular disease enrichment analysis revealed that the same set of signature genes associated with dALFF levels was enriched for multiple neurological biological processes. Finally, genetic profiling of individual modules identified multiple core genes closely related to schizophrenia, also potentially associated with neuronal activity. Thus, this paper explores genetic features of brain regions in the schizophrenia closely related to low-frequency amplitude ratio levels based on imaging genetics, which suggests structural endophenotypes associated with schizophrenia.