Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap

Published February 9, 2018 in Science, Gandal, Haney, et al

Research led by Daniel Geschwind of the University of California, Los Angeles used postmortem brain tissue, including resources from Autism BrainNet, found similar gene expression patterns in the brains of those with autism, schizophrenia, and bipolar disorder. All three conditions show an activation of genes in star-shaped brain cells called astrocytes, and suppression of genes that function at synapses, the junctions between neurons. The autism brains also show a unique increase in the expression of genes specific to immune cells called microglia. Below is the abstract from the report, followed by a link to the full text.

Abstract

The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how genetic variants impart brain dysfunction or pathology. We used transcriptomic profiling as a quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders—autism, schizophrenia, bipolar disorder, depression, and alcoholism—compared with matched controls. We identified patterns of shared and distinct gene-expression perturbations across these conditions. The degree of sharing of transcriptional dysregulation is related to polygenic (single-nucleotide polymorphism–based) overlap across disorders, suggesting a substantial causal genetic component. This comprehensive systems-level view of the neurobiological architecture of major neuropsychiatric illness demonstrates pathways of molecular convergence and specificity.

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