- Gandal, Michael J
- Haney, Jillian R
- Parikshak, Neelroop N
- Leppa, Virpi
- Ramaswami, Gokul
- Hartl, Chris
- Schork, Andrew J
- Appadurai, Vivek
- Buil, Alfonso
- Buil, Alfonso
- Werge, Thomas M
- Liu, Chunyu
- White, Kevin P
- CommonMind Consortium
- PsychENCODE Consortium
- iPSYCH-BROAD Working Group
- Horvath, Steve
- Geschwind, Daniel H
- et al.
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.