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Gene expression represents a fundamental interface between genes andenvironment in the development and ongoing plasticity of the human organism.Individual differences in gene expression are likely to underpin much of humandiversity, including psychiatric illness. Gene expression shows a distinctregulatory pattern in different tissues. Therefore, brain tissue analysisprovides insights into brain disorder mechanisms. Furthermore, mechanisticunderstanding of gene regulatory pattern can be provided through studying theunderlying relationships as a complex network. Identification of brain specificgene relationships provides a complementary framework in which to tackle thecomplex dysregulations that occur in neuropsychiatric and other neurologicaldisorders. Using a systems approach established in Mendelian randomization andBayesian Network, we integrated genetic and transcriptomic data from thecommon-mind consortium and identified transcriptomic causal networks inobservational studies. Focusing on Schizophrenia disorder, we identified highimpact genes and revealed their underlying pathways in brain tissue. Inaddition, we generated novel hypotheses including genes as causes of theschizophrenia-associated genes and new genes associated with Schizophrenia.This approach may facilitate a better understanding of the disease mechanismthat is complementary to molecular experimental studies especially for complexsystems and large-scale data sets.

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