In this week's Science, Science Translational Medicine, and Science Advances, members of the PsychENCODE Consortium present 10 studies examining the molecular mechanisms of neuropsychiatric disorders including schizophrenia, bipolar disorder, and autism spectrum disorder. In one Science study, researchers use a variety of techniques to profile gene expression, epigenetic modifications, and regulatory elements in different brain regions and cell types across the course of brain development. In another, brain tissue and single-cell data from nearly 2,000 individuals is integrated into a deep-learning model to improve disease risk prediction. In a third paper, investigators integrate genotypes and RNA sequencing in brain samples from nearly 1,700 individuals to perform a transcriptome-wide characterization of the molecular pathology of autism, schizophrenia, and bipolar disorder. Also in Science are reports into spatiotemporal transcriptomic divergence across human and macaque brain development; the transcriptomic and epigenomic landscape of human cortical development modeled in organoids; neuron-specific signatures in the chromosomal connectome associated with schizophrenia risk; and genome-wide de novo risk score and promoter variation in autism spectrum disorder.
In Science Translational Medicine, PsychENCODE investigators also analyze microRNA expression in brain tissue from schizophrenia and bipolar disorder patients, as well as controls. They find that individuals with the disorders differentially express a coexpression network module containing genes that are principally involved in glial and neural cell genesis and glial cell differentiation, and including schizophrenia risk genes carrying rare variants. One gene linked to bipolar disorder was found to regulate the module, although additional research is needed to determine the causative role of the gene. In another paper, PsychENCODE scientists investigate the role of rare copy number variations in schizophrenia risk. A genome-wide analysis of 296 brain samples from controls reveals a long, non-coding RNA located in a chromosomal deletion region associated with schizophrenia risk that proved to be a "hub gene" for a number of other genes related to the disorder.
And in Science Advances, a PsychENCODE team reports a three-dimensional epigenomic map of primary cultured neuronal cells derived from olfactory neuroepithelium, which hold potential as an epigenetic model for certain brain disorders. The work "not only provides a framework for understanding individual epigenetic variation using a primary cell model system, but also contributes valuable data resources for epigenomic studies of neuronal epithelium," the reserachers conclude.
GenomeWeb has more on this collection of papers, here.