Identification of Schizophrenia Related Biological Pathways Across Eight Brain Regions

Schizophrenia is a severe mental disorder with high heritability. GWAS had identified multiple susceptible regions associated with schizophrenia. However, a number of variants remained to be explored due to their location in non-coding regions. Enhancers were important DNA elements that positively regulated the expression of target genes. We applied a novel method to conduct pathway enrichment analysis in schizophrenia across 8 brain regions. GWAS summary data and enhancer-target networks of the 8 regions were integrated in this approach. Finally, we identified several genes involving in neurodevelopmental processes across the 8 regions. It is remarkable germinal matrix showed strongest relationship with schizophrenia, which is mainly involved in cells migrate out during brain development. Substantia nigra, dorsolateral prefrontal cortex, inferior temporal lobe and hippocampus middle also showed stronger signals. We also found that schizophrenia was mainly associated with "Immune Diseases", "Gene Expression", "Cell Cycle", "Cellular Component" and "Biological Process" across specific brain regions. Our study supported the argument that schizophrenia is a severe mental disorder with early brain dysplasia or impairment of cognitive and memory related areas, which provided novel insight to the pathophysiology of schizophrenia.