Shared Molecular Neuropathology Across Major Psychiatric Disorders Parallels Polygenic Overlap

• DOI: 10.1176/appi.focus.17103
• Publication Date: 2019-01-10T08:12:18Z
• Authors: Michael J. Gandal; Jillian R. Haney; Neelroop N. Parik...; Virpi Leppa; Gokul Ramaswami; Chris Hartl; Andrew J. Schork; Vivek Appadurai; Alfonso Buil; Thomas M. Werge; Chunyu Liu; Kevin P. White; ; Daniel H. Geschwind
• Keywords: Neuropathology; Psychiatric genetics

The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how variants impart brain dysfunction or pathology. We used transcriptomic profiling as quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders—autism, schizophrenia, bipolar disorder, depression, alcoholism—compared with matched controls. identified patterns shared distinct gene-expression perturbations these conditions. degree sharing transcriptional dysregulation related polygenic (single-nucleotide polymorphism–based) overlap disorders, suggesting substantial causal component. This comprehensive systems-level view the neurobiological architecture illness demonstrates pathways convergence specificity. (Gandal et al., "Shared neuropathology disorders parallels overlap" Science 09 Feb 2018:Vol. 359, Issue 6376, pp. 693-697 (DOI: 10.1126/science.aad6469). Reprinted permission from AAAS)