A Perspective of the Cross-Tissue Interplay of Genetics, Epigenetics, and Transcriptomics, and Their Relation to Brain Based Phenotypes in Schizophrenia

Genetic association studies of psychiatric disorders have provided unprecedented insight into disease risk profiles with high confidence. Yet, the next research challenge is how to translate this rich information into mechanisms of disease, and further help interventions and treatments. Given other comprehensive reviews elsewhere, here we want to discuss the research approaches that integrate information across various tissue types. Taking schizophrenia as an example, the tissues, cells, or organisms being investigated include postmortem brain tissues or neurons, peripheral blood and saliva, in vivo brain imaging, and in vitro cell lines, particularly human induced pluripotent stem cells (iPSC) and iPSC derived neurons. There is a wealth of information on the molecular signatures including genetics, epigenetics, and transcriptomics of various tissues, along with neuronal phenotypic measurements including neuronal morphometry and function, together with brain imaging and other techniques that provide data from various spatial temporal points of disease development. Through consistent or complementary processes across tissues, such as cross-tissue methylation quantitative trait loci (QTL) and expression QTL effects, systemic integration of such information holds the promise to put the pieces of puzzle together for a more complete view of schizophrenia disease pathogenesis.