Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap
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- 9 February 2018
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 359 (6376), 693-697
- https://doi.org/10.1126/science.aad6469
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.Keywords
Funding Information
- National Institute of Mental Health (MH106438)
- National Institute of Mental Health (MH094714)
- National Institute of Mental Health (MH103339)
- National Institute of Mental Health (MH110920)
- National Institute of Mental Health (MH103340)
- Simons Foundation (206733)
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