Insights into Complex Brain Functions Related to Schizophrenia Disorder through Causal Network Analysis

Gene expression represents a fundamental interface between genes and environment in the development and ongoing plasticity of the human organism. Individual differences in gene expression are likely to underpin much of human diversity, including psychiatric illness. Gene expression shows a distinct regulatory pattern in different tissues. Therefore, brain tissue analysis provides insights into brain disorder mechanisms. Furthermore, mechanistic understanding of gene regulatory pattern can be provided through studying the underlying relationships as a complex network. Identification of brain specific gene relationships provides a complementary framework in which to tackle the complex dysregulations that occur in neuropsychiatric and other neurological disorders. Using a systems approach established in Mendelian randomization and Bayesian Network, we integrated genetic and transcriptomic data from the common-mind consortium and identified transcriptomic causal networks in observational studies. Focusing on Schizophrenia disorder, we identified high impact genes and revealed their underlying pathways in brain tissue. In addition, we generated novel hypotheses including genes as causes of the schizophrenia-associated genes and new genes associated with Schizophrenia. This approach may facilitate a better understanding of the disease mechanism that is complementary to molecular experimental studies especially for complex systems and large-scale data sets.